Evolution and Variation in Folded Proteins

As a general rule, the primary structure of a protein (amino acid sequence) ultimately determines it's final three-dimensional shape¹. Proteins fold spontaneously to adopt a specific structure that minimizes free energy. The folded protein occupies the bottom of a free energy well [How Proteins Fold, The Anfinsen Experiment in Protein Folding, Disulfide Bridges Stabilize Folded Proteins, Heat Shock and Molecular Chaperones].

Each protein has a characteristic shape associated with its function. When we discuss the evolution of proteins, we like to divide the residues into three categories as shown below for the structure of myoglobin from sperm whale (Physeter catodon) [PDB 1A6M].

Myoglobin is a small protein with a bound heme group (shown as a space-filling molecule). It carries oxygen in the bloodstream and tissues. The oxygen molecule binds to the active site of the protein near one side of the heme group. There are specific amino acid residues at the active site that are absolutely required for binding oxygen. As you might expect, these amino acids are highly conserved—they will be found at that position in myoglobin from humans or any other species.

The second category of amino acid residues makes up the hydrophobic interior of the protein. Myoglobin is an all-α-helical protein and several of the helices group together to form a helix bundle. The interior of that bundle consists largely of hydrophobic amino acid residues. This is what stabilizes the three-dimensional structure and causes the polypeptide chain to spontaneously fold after it is synthesized.

The third category of residues is the surface residues. These are usually hydrophilic residues that interact with the surrounding water. The surface residues don't make as much of a contribution to the overall three-dimensional structure so their exact composition can be quite variable.

The class of proteins to which myoglobin belongs is called "globins." There are two other globins that you are probably familiar with: α-globin and β-globin are the two polypeptides that come together to form an α₂β₂ hemoglobin tetramer.

The three proteins (myoglobin, α-globin, and β-globin) descended by gene duplication from a common ancestral globin several hundred million years ago. Today their amino acid sequences are quite different due to the accumulation of random mutations and fixation by random genetic drift. In spite of the differences in primary structure, the three-dimensional structures of the three proteins are very similar. This can easily be shown by superimposing the three structures as shown in the figure (myoglobin=green, α-globin=blue, β-globin=purple).

Most people don't appreciate the amount of variation that underlies this conserved three-dimensional structure. It's worth taking a look at a bunch of aligned globin sequences from different species to see exactly which amino acids are highly conserved and which positions can tolerate almost any amino acid.

Let's go to the Pfam (protein family) database at the Sanger Institute in Cambridge (UK). The entry for the globin family is Globin PF00041. Click on "Alignments" in the left sidebar. This link takes you to the alignment page where you can create an alignment of all the known globin sequences. Choose 75 seeds (default) in the first table and select "Pfam viewer" from the pull-down menu under "Viewer." Click "View" to see the alignments.

Highly conserved amino acid residues are highlighted by vertical shading in the Pfam view. The first thing you should notice is that there are very few amino acids that are invariant. The conserved residue on the left (blue) is tryptophan (W). It's present in most of the globins from different species but not all. Look at the other positions and note that in most cases a variety of different amino acid residues can be substituted. Sometimes only hydrophobic residues (blue) can be found at a particular site and sometimes there are other restricted choices. Lots of insertions and deletions (dots) can be tolerated without major disruption to the overall three-dimensional structure.

Data like this reveals that the amino acid residues in the active site are usually conserved. Residues in the hydrophobic core are moderately conserved. And residues on the surface are hardly conserved at all.

The point is that there are literally billions of different proteins that have the same shape as globins and still function as carriers of oxygen. This is an important point. Opponents of evolution often take a single globin from a single species and calculate the probability that such a structure will form. They assume that only one out of twenty amino acids can be found at each position and the resulting probability (e.g., 200²⁰) is enormous. Thus, they conclude, such a protein could never form by chance. They don't seem to appreciate the fact that we already know of billions of different proteins that can function as globins.

There are many other examples of this observation. The four structures below show the conformation of the cytochrome c polypeptide chain from tuna, rice, yeast, and a bacterium. The amino acid sequences have diverged considerably from their common ancestor of 3 billion years ago but the structures are very similar.

We conclude that the amino acid sequence of a polypeptide determines how it will fold in three-dimensional space but there are billions of different amino acid sequences that will adopt the same structure.

Finally, let's look at a more complicated example. The enzymes lactate dehydrogenase (below left) and malate dehydrogenase (below right) share a common ancestor even though they are different enzymes. This is a case where substitutions of amino acid residues in the active site gave rise to a new activity. Today the amino acid sequence similarity is barely above the threshold for defining homology but the structures are still very similar.

---

1. Other factors that contribute are bound ligands, such as heme groups, and interactions with other proteins as in multimeric proteins with sifferent subunits.

Escalators Are Dangerous

 
From Science News [Rate Of Escalator Injuries To Older Adults Has Doubled]

Using U.S. Consumer Product Safety Commission data, the researchers found nearly 40,000 older adults were injured on escalators between 1991 and 2005. The most frequent cause of injury was a slip, trip or fall resulting in a bruise or contusion. The most common injuries were to the lower extremities. However, most injuries were not serious. Only 8 percent of the 39,800 injured were admitted to the hospital after evaluation in an emergency department.

"Although escalators are a safe form of transportation, fall-related injuries do occur. Older adults, especially those with mobility, balance or vision problems, should use caution while riding an escalator and especially when stepping on or off. They should not try to walk up or down a moving escalator, carry large objects, or wear loose shoes or clothing while riding since these appear to be associated with an increased risk of falling," said Dr. O'Neil, associate professor of clinical pediatrics at the IU School of Medicine.

---

500,000 Visitors

 
Sometime on Wednesday night Sandwalk notched up 500,000 visitors. To put this in perspective, after 16 months of blogging the total number of visitors is less than half the number who visit Pharyngula in one month.

This is depressing. We need to do something about it. Is there any way we can shut down Pharyngula?

---

Fractal Wrongness

 

From Kuenwoo Lee (may not be original) ...

Fractal Wrongness

The state of being wrong at every conceivable scale of resolution. That is, from a distance, a fractally wrong person's worldview is incorrect; and furthermore, if you zoom in on any small part of that person's worldview, that part is just as wrong as the whole worldview.

Debating with a person who is fractally wrong leads to infinite regress, as every refutation you make of that person's opinions will lead to a rejoinder, full of half-truths, leaps of logic, and outright lies, that requires just as much refutation to debunk as the first one. It is as impossible to convince a fractally wrong person of anything as it is to walk around the edge of the Mandelbrot set in finite time.

If you ever get embroiled in a discussion with a fractally wrong person on the Internet--in mailing lists, newsgroups, or website forums--your best bet is to say your piece once and ignore any replies, thus saving yourself time.

---

The image is "borrowed" from Jeffrey Shallit's blog Recursivity [Fractal Wrongness]

Examples of Protein Structure

Here's a slideshow of figures from Horton et al. (2006) showing cartoons of various proteins. At first it seems as though every protein is completely different but after a while you begin to notice that there are recurring motifs—especially β sheets in the hydrophobic core of a domain.



Click here to see a full-screen version of the slideshow. More adventuresome readers might want to visit the actual structures on the Protein Data Base (PDB). Here are the links to each PDB record. References to the people who solved the structure can be found in the PDB record.

• Human (Homo sapiens) serum albumin [PDB 1BJ5] (class: all-α). This protein has several domains consisting of layered α helices and helix bundles.
• Escherichia coli cytochrome b₅₆₂ [PDB 1QPU] (class: all-α). This is a heme-binding protein consisting of a single four-helix bundle domain.
• Escherichia coli UDP N-acetylglucosamine acyl transferase [PDB 1LXA] (class: all-β). The structure of this enzyme shows a classic example of a β-helix domain.
• Jack bean (Canavalia ensiformis) concanavalin A [PDB 1CON] (class: all-β). This carbohydrate-binding protein (lectin) is a single-domain protein made up of a large β-sandwich fold.
• Human (Homo sapiens)peptidylprolyl cis/trans isomerase [PDB 1VBS] (class: all-β). The dominant feature of the structure is a β-sandwich fold.
• Cow (Bos taurus) γ crystallin [PDB 1A45] (class: all-β) This protein contains β-barrel two domains.
• Jellyfish (Aequorea victoria) green fluorescent protein [PDB
  1GFL] (class: all-β). This is a β-barrel structure with a central α helix. The strands of the sheet are antiparallel.
• Pig (Sus scrofa) retinol-binding
  protein [PDB 1AQB] (class: all-β). Retinol binds in the interior of a β-barrel fold.
• Brewer’s yeast (Saccharomyces carlsburgensis) old yellow enzyme
  (FMN oxidoreductase) [PDB 1OYA] (class: α/β). The central fold is an α/β barrel with parallel β strands connected by α helices. Two of the connecting regions are highlighted in yellow.
• Escherichia coli enzyme required for tryptophan biosynthesis [PDB 1PII] (class: α/β). This is a bifunctional enzyme containing two distinct domains. Each domain is an example of an α/β barrel. The left-hand domain contains the indolglycerol phosphate synthetase activity, and the right-hand domain contains the phosphoribosylanthranilate isomerase activity.
• Pig (Sus scrofa) adenylyl kinase [PDB 3ADK] (class: α/β). This single-domain protein consists of a five-stranded parallel β sheet with layers of α helices above and below the sheet. The substrate binds in the prominent groove between helices.
• Escherichia coli flavodoxin [PDB 1AHN] (class: α). The fold
  is a five-stranded parallel twisted sheet surrounded by α helices.
• Human (Homo sapiens) thioredoxin [PDB 1ERU] (class: ). The structure of this protein is very similar to that of E. coli flavodoxin except that the five-stranded twisted sheet in the thioredoxin fold contains a single antiparallel strand.
• Escherichia coli L-arabinose-binding protein [PDB 1ABE] (class: α/β). This is a two-domain protein where each domain is similar to
  that in E. coli flavodoxin. The sugar L-arabinose binds in the cavity between the two domains.
• Escherichia coli DsbA (thiol-disulfide oxidoreductase/disulfide isomerase) [PDB 1A23] (class: α/β). The predominant feature of this structure is a (mostly) antiparallel β sheet sandwiched between α helices. Cysteine side chains at the end of one of the α helices are shown (sulfur atoms are yellow).
• Neisseria gonorrhea pilin [PDB 2PIL] (class: α + β). This polypeptide is one of the subunits of the pili on the surface of the bacteria responsible for gonorrhea. There are two distinct regions of the structure: a β sheet and a long α helix.
• Chicken (Gallus gallus) triose phosphate isomerase [PDB 1TIM]. This protein has two identical subunits with α/β barrel folds.
• HIV-1 aspartic protease [PDB 1DIF]. This protein has two identical all-β subunits that bind symmetrically. HIV protease is the target of many new drugs designed to treat AIDS patients.
• Streptomyces lividans potassium channel protein [PDB 1BL8]. This membrane-bound protein has four identical subunits, each of which contributes to a membrane-spanning eight-helix bundle.
• Bacteriophage MS2 capsid protein [PDB 2MS2]. The basic unit of the MS2 capsid is a trimer of identical subunits with a large β sheet.
• Human (Homo sapiens) hypoxanthine-guanine phosphoribosyl transferase (HGPRT) [PDB 1BZY]. HGPRT is a tetrameric protein containing two different types of subunit.
• Rhodopseudomonas viridis photosystem [PDB 1PRC]. This complex, membrane-bound protein has two identical subunits (orange, blue) and two other subunits (purple, green) bound to several molecules of photosynthetic pigments.

---

Horton, H.R., Moran, L.A., Scrimgeour, K.G., perry, M.D. and Rawn, J.D. (2006) Principles of Biochemisty. Pearson/Prentice Hall, Upper Saddle River N.J. (USA)

Levels of Protein Structure

There are four levels of protein structure. The primary structure refers to the sequence of amino acid residues in the polypeptide chain written left-to-right from the N-terminus to the C-terminus.

Secondary structures are ordered structures formed by internal hydrogen bonding between amino acid residues. The common secondary structures are the α helix, the β strand, and various loops and turns. The β sheet is often counted as secondary structure although, strictly speaking, it is a motif (see below).


The tertiary structure of a polypeptide is the three-dimensional conformation. Typical proteins contain α helices, β strands, and turns, although there are some proteins that only have α helices and turns, and others that have only β sheets and turns. In many cases, the final structure consists of distinct, independently folded regions called domains.

An example of a protein with multiple domains is shown on the left. This protein is the enzyme pyruvate kinase from cat (Felix domesticus). There are three separate domains indicated by the square brackets on the side. Note that each of the domains is connected to another by a short stretch of unordered polypeptide chain.

In some cases, a particular domain is shared by several proteins suggesting that different proteins can be formed by combining various domains that evolved separately. In other cases, similar domain structures might arise independently by convergent evolution.

Quaternary structure only applies to proteins that are composed of more than one polypeptide chain. Each of the polypeptides is called a subunit. The subunits might be identical, as in the example shown above, or they might be very different as in my favorite enzyme ubiquinone:cytochrome c oxidoreductase (complex III).

There are certain motifs that occur over and over again in different proteins. The helix-loop-helix motif, for example, consists of two α helices joined by a reverse turn. The Greek key motif consists of four antiparallel β strands in a β sheet where the order of the strands along the polypeptide chain is 4, 1, 2, 3. The β sandwich is two layers of β sheet [see β Strands and β Sheets].

The vast majority of motifs do not have a common evolutionary origin in spite of many claims to the contrary. They arise independently and converge on a common stable structure. The fact that these same motifs occur in hundreds of different proteins indicates that there are a limited number of possible folds in the universe of protein structures. The original primitive protein may have been relatively unstructured but over time there will be selection for more and more stable structures. This selection will favor the common motifs.

Larger motifs are often called domain folds because they make up the core of a domain. The parallel twisted sheet is found in many domains that have no obvious relationship other than the fact that they share this very stable core structure. The β barrel structure is found in many membrane proteins. There are dozens of enzymes that have adapted to an α/β barrel. These enzymes are not evolutionarily related. (The β helix is much less common.)

---

[Figure Credit: The figures are from Horton et al. (2006)]

Horton, H.R., Moran, L.A., Scrimgeour, K.G., perry, M.D. and Rawn, J.D. (2006) Principles of Biochemisty. Pearson/Prentice Hall, Upper Saddle River N.J. (USA)

Loops and Turns

In addition to α helices and β strands, a folded polypeptide chain contains two other types of secondary structure called loops and turns. (There are also regions of unordered structure, often called coils.)

Loops and turns connect α helices and β strands. The most common types cause a change in direction of the polypeptide chain allowing it to fold back on itself to create a more compact structure.

Loops are not well defined. They generally have hydrophilic residues and they are found on the surface of the protein. Loops that have only 4 or 5 amino acid residues are called turns when they have internal hydrogen bonds. Reverse turns are a form of tight turn where the polypeptide chain makes a 180° change in direction. Reverse turns are also called β turns because they usually connect adjacent β strands in a β sheet.

Reverse turns. (left) Type I β turn. The structure is stabilized by a hydrogen bond between the carbonyl oxygen of the first N-terminal residue (Phe) and the amide hydrogen of the fourth residue (Gly). Note the proline residue at position n + 1 (right) Type II β turn. This turn is also stabilized by a hydrogen bond between the carbonyl oxygen of the first N-terminal residue (Val) and the amide hydrogen of the fourth residue (Asn). Note the glycine residue at position n + 2 [PDB 1AHL (giant sea anemone neurotoxin)]. (Horton et al. 2006)

The two most common common types of β turn are the type I and type II turns shown above. The key point about turns is that they are highly ordered structures stabilized by internal hydrogen bonds. This is why they are counted as the third form of secondary structure (along with the α helix and β strand).

---

Horton, H.R., Moran, L.A., Scrimgeour, K.G., perry, M.D. and Rawn, J.D. (2006) Principles of Biochemisty. Pearson/Prentice Hall, Upper Saddle River N.J. (USA)

Nobel Laureates: Sir William Henry Bragg and Lawrence Bragg

 

The Nobel Prize in Physics 1915.

"for their services in the analysis of crystal structure by means of X-rays"


In 1915, Sir William Henry Bragg (1862 - 1942) and William Lawrence Bragg (1890 - 1971) were awarded the Nobel Prize in Physics for their work on the structure of crystals as determined by X-ray crystallography. The Physics prize in 1914 had been awarded to Max von Laue for his discovery of the diffraction of X-rays by crystals.

In order to solve the structure of a crystal, two advances were necessary. First, the senior Bragg developed an X-ray spectrometer that produced a monochromatic (single frequency) beam of X-rays of the desired strength. Second, his son Lawrence, worked out the mathematics of the diffraction in order to relate the pattern of diffraction images to the underlying structure. Part of this solution is the Bragg Equation or Bragg's Law.

After World War II, William Lawrence Bragg (then Sir Lawrence Bragg) became head of the Cavendish Laboratory in Cambridge. He rapidly transformed the laboratory into a center or the study of biological molecules. Bragg was responsible for hiring several future Nobel laureates including Max Perutz, John Kendrew, and Fred Sanger. Francis Crick and Jim Watson were also part of this group [see The Storyof DNA: Part 1].

The Braggs were the first Australians to win Nobel Prizes. Lawrence Bragg was the youngest person to win a Nobel Prize (he was 25 years old in 1915). The Braggs are the only father and son team to share a Nobel Prize. (Can anyone name the other parent/sibling pair(s) to win separate Nobel Prizes?)

The presentation speech was delivered by Professor G. Granqvist, Chairman of the Nobel Committee for Physics of the Royal Swedish Academy of Sciences.
THEME:

Nobel Laureates

Von Laue's epoch-making discovery of the diffraction of the X-rays in crystals, on the one hand established wave motion as the essential quality of those rays and, on the other, afforded the experimental proof of the existence of molecular gratings in the crystals. The problem, however, of calculating the crystal structures from von Laue's formulae was an exceedingly complicated one, in as much as not only the space lattices, but also the wavelengths and the intensity-distribution over the various wavelengths in the spectra of the X-rays, were unknown quantities. It was consequently a discovery of epoch-making significance when W.L. Bragg found out that the phenomenon could be treated mathematically as a reflection by the successive parallel planes that may be placed so as to pass through the lattice points, and that in this way the ratio between the wavelengths and the distances of the said planes from each other can be calculated by a simple formula from the angle of reflection.

It was only by means of that simplification of the mathematical method that it became possible to attack the problem of the crystal structures, but to attain the end in view it was further necessary that the photographic method employed by von Laue should be replaced by an experimental one, based on the reflection principle, which admitted of a definite, even though at first unknown, wavelength being made use of. The instrument requisite for the said purpose, the so-called X-ray spectrometer, was constructed by Professor W.H. Bragg, W.L. Bragg's father, and it has been with the aid of that instrument that father and son have carried out, in part conjointly, in part each on his own account, a series of extremely important investigations respecting the structure of crystals.

If a number of cubes are laid on and beside each other in such a way that one cube face coincides in every case with the face of an adjoining cube, whereby consequently eight vertices always meet in one point, those angular points give a visual picture of the lattice points in the so-called simple cubic lattice. If again a lattice point is placed so as to coincide with the central point of each cube face, the so-called face-centred cubic lattice is obtained, whereas the centred cubic lattice has one lattice point in every cube-centre. With the exception of these three cases there is no cubic lattice that fulfils the condition that parallel planes placed in any direction whatever so as to pass through all the lattice points, shall also be at a constant distance from each other. The space lattice in the regular or cubic system must therefore coincide with one of those three, or constitute combinations of them. In such lattice combinations, on the other hand, in which the condition just mentioned is not fulfilled, where consequently parallel planes placed to pass through all the lattice points in certain directions are not equidistant, that circumstance is revealed by an abnormal intensity distribution among spectra of different orders, when the reflection takes place by those planes.

From crystallographical data it is always known how the face of a cube is situated in any given regular crystal, and there is consequently no difficulty in fixing the crystal on the spectrometer table in such a way that the reflection shall take place by planes with any prescribed orientation.

The rays falling on the crystal were produced by X-ray tubes, platinum being at first used for the anticathode. The characteristic X-radiation of the metals consists, as is well known, of a few strong lines or narrow bands, and the very first experiments with the spectrometer revealed the X-radiation that is characteristic of platinum. However, in the research undertaken to find out the nature of complicated space lattices, in which an abnormal intensity distribution among spectra of varying orders constitutes one of the most important of the results observed, it soon proved desirable to have available an X-radiation of approximately half the wavelength of the strongest platinum-line. From theoretical considerations W.H. Bragg regarded it as probable that a metal whose atomic weight was somewhere near the figure 100, would give a characteristic radiation of the desired wavelength. Accordingly anticathodes of palladium and rhodium were produced, which fully answered the purpose in view, so that spectra ev en of the fifth order could be obtained and measured. In order to take practical advantage, however, of those results, it was essential to have a method for calculating the intensity in the case of a complicated space lattice, that would prove simpler than the one given by von Laue's theory, and W.L. Bragg developed one.

The above is a brief sketch of the methods discovered by the two Braggs for investigating crystal structures. The results of their investigations embrace a large number of crystals belonging to various systems and can only be cursorily summarized in this place.

To begin with, the two investigators applied themselves to the simplest types of the regular system, represented by the alkaline haloid salts. It then proved that potassium bromide and potassium iodide showed the spectra that are characteristic of a face-centred cubic lattice, while the spectra of potassium chloride represented a simple cubic lattice, sodium chloride occupying an intermediate position. As it must be assumed, on the strength of the analogy of these salts, both in a chemical and a crystallographical sense, that they are possessed of a corresponding space lattice, which could also be corroborated in another way, it was proved by those researchers that the lattice of the crystals in question consists of two face-centred cubic lattices corresponding to the two atoms, which interpenetrate in such a way that they together constitute one single cubic lattice.

From these investigations it follows that a metal atom in the crystals of the alkaloid salts is situated at one and the same distance from the six haloid atoms nearest to it, and vice versa - a relationship that was found to prevail, mutatis mutandis, in all the crystals examined. That means the exceedingly important discovery, both for molecular physics and chemistry, that the crystals consist of atomic lattices and not, as has been always imagined, of molecular ones.

Two face-centred cubic lattices can also interpenetrate in such a way that every point belonging to the one lattice is at the centre of gravity of a tetrahedron whose vertices are points belonging to the other lattice. That structure was found by the two Braggs in the diamond, and afforded an experimental support for the tetrahedral arrangement that chemists postulate for the four-coordinate carbon. On the other hand, the explanation became evident of why crystallographers have not been able to agree regarding the class in the regular system to which the diamond should be referred.

It would carry us too far and be quite too complicated a proceeding to give an account here of the further investigations into the space lattices of the crystals. It will suffice to add that, in the course of their investigations, the two Braggs have also discovered important relations between the amplitude and the phase difference of the diffracted rays on the one hand and the atomic weights on the other, and have also shown experimentally the influence of heat on the space lattice.

Finally it may be mentioned that the two investigators have also determined the wavelengths of the X-rays and the distances between the successive planes placed to pass through the lattice points with such exactitude, that the error, if any, is probably a t most some few units per cent and is more due to the general physical constant entering into the calculations than to the measurements themselves.

Thanks to the methods that the Braggs, father and son, have devised for investigating crystal structures, an entirely new world has been opened and has already in part been explored with marvellous exactitude. The significance of these methods, and of the results attained by their means, cannot as yet be gauged in its entirety, however imposing its dimensions already appear to be. In consideration of the great importance that these methods possess for research in the realm of physics, the Swedish Royal Academy of Sciences decided that the 1915 Nobel Prize in Physics should be divided between Professor W.H. Bragg and his son W.L. Bragg, in recognition of their services in promoting the investigation of crystal structures by means of X-rays.

---

β Strands and β Sheets

 
The &alpha helix is one form of secondary structure in proteins. When a polypeptide chain contains the right sequence of amino acids it can adopt a helical conformation.

There are other conformations commonly found in proteins. One of them is the β structure, which is characterized by long extended polpeptide chains in contrast to the compact helix of the α helix. Single β strands are rarely found in proteins because the structure is not that much more stable than a random coil. However, when two adjacent β strands line up they can from bridges of hydrogen bonds. This creates a very stable structure known as a β sheet. In the example shown (left) three parallel β strands line up edge to edge to form a highly stable sheet with multiple hydrogen bond (shown in yellow).

β sheets can also be formed when antiparallel β strands align edge to edge. As a matter of fact, the antiparallel conformation is more stable, and more common, than the parallel conformation.

β strands are usually drawn as wide arrows with the tip of the arrow head representing the C-terminal end of the polypeptide chain. As shown in the cartoon on the right, the strands are often twisted and the amino acid side chains project above and below the plane of the β strand.

The amino acid composition of β strands tends to favor hydrophobic (water fearing) amino acid residues. The side chains of these residues tend to be less soluble in water than those of more hydrophilic (water loving) residues. As you might imagine, β structures tend to be found inside the core structure of proteins where the hydrogen bonds between strands are protected from competition with water molecules.

One of the common motifs in proteins is the β sandwich, formed when two β sheets are stacked on top of one another. The example shown below is the coat protein of grass pollen grains [PDB 1BMW]. For those people who are allergic to grass pollen, this protein is the main culprit. This example is the simplest form of a β sandwich since each sheet consists of only two β strands.



In order to appreciate why this is such a stable (and common) motif we need to add in the amino acid side chains. (They are usually ignored in the kinds of structures shown above so we can trace the polypeptide backbone.) In the figure on the right I've drawn the hydrophobic side chains in blue so you can see how they cluster together to form the interior "filling" of the sandwhich. You can think of these hydrophobic regions as being like the oil in a mixture of oil and water. The oil droplets tend to come together to exclude the water molecules. Similarly, the hydrophobic residues tend to come together in the middle of the protein and exclude water molecules. This is called hydrophobic interaction and it's one of the dominent weak forces n biochemistry.

Most proteins are made up of combinations of α helices and β strands. The third kind of secondary structure is turns.

---

[Figures are from Horton et al. (2006) © Laurence A. Moran, Pearson/Prentice Hall]

Horton, H.R., Moran, L.A., Scrimgeour, K.G., perry, M.D. and Rawn, J.D. (2006) Principles of Biochemisty. Pearson/Prentice Hall, Upper Saddle River N.J. (USA)

Monday's Molecule #64

 
Today's molecule isn't really a molecule. It's an indirect representation of a molecule. It would be amazing if one of you could guess the molecule by looking at the figure but that's probably beyond the ability of most Sandwalk readers. (I know I can't do it.) Your task is to identify what that strange picture is all about and how is it generated.

There's a direct connection between this image and Wednesday's Nobel Laureate(s). Your second task is to figure out the significance of today's photograph and identify the Nobel Laureate(s) who is associated with discovering the technique. (Be sure to check previous Laureates.)

The reward goes to the person who correctly identifies the technique and the Nobel Laureate(s). In addition, you must identify what is unique about this particular Nobel Prize.

Previous winners are ineligible for one month from the time they first collected the prize. There is only one ineligible candidate for this week's reward. The prize is a free lunch at the Faculty Club.

THEME:

Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the structure and the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureates so you might want to check the list of previous Sandwalk postings.

Correct responses will be posted tomorrow along with the time that the message was received on my server. I may select multiple winners if several people get it right.

Comments will be blocked for 24 hours. Comments are now open.

UPDATE: We have a winner! There were several dozen readers who knew that this was a photograph of an X-ray diffraction pattern. Several of them knew that the crystal was sodium chloride. Many of them guessed correctly that the Nobel Laureates were the Braggs—the first, and only, father and son team to win a Nobel Prize together. The first person to send all of this information in an email message was Andre Macphail. He wins a free lunch at the Faculty Club. Unfortunately, he lives in France so he won't be able to make it anytime soon. He's taking a rain check.

---

My God Delusion Index Is Zero, What's Yours?

 

---

[Hat Tip: Muse in vivo]

The Austrian Evolution Summit: The Invitation and Outline

Susan Mazur has followed up on her previous article about the upcoming conference on evolution [see Don't Throw the Baby Out with the Bathwater]. She has now published the original invitation to the conference and the first outline of the program [The Invite -- "Altenberg 16" Evolution Summit]. If you're interested in what needs to be in a new extended evolutionary theory, then get on over to Scoop and read the invitation.

Here's what the Alternberg 16 are going to talk about ...

SELECTION AND ADAPTATION REFORMED
* Drift: John Beatty, University of British Columbia
* Neutralism: Sergey Gavrilets, University of Tennessee
* Multilevel selection: David Sloan Wilson, Binghamton University

NEW VIEWS ON GENOMES AND INHERITANCE
* Gene regulatory networks: Greg Wray, Duke University
* Genomes and post-genomes: Michael Purugganan, New York University
* Epigenetic inheritance: Eva Jablonka, Tel-Aviv University
* Niche inheritance: John Odling-Smee, Oxford University

UNDERSTANDING THE PHENOTYPE
* Dynamics of macroevolution: David Jablonski, University of Chicago
* Phenotypic plasticity: Massimo Pigliucci, Stony Brook University
* Origins of form: Stuart Newman, New York Medical College

CONTRIBUTIONS FROM EVO-DEVO
* Innovation: Gerd Müller, University of Vienna
* Modularity: Günter Wagner, Yale University
* Evolvability: Marc Kirschner, Harvard University

CHARACTERISTICS OF EXTENDED SYNTHESIS
* Non-centrality of the gene: Werner Callebaut, Hasselt University
* Principles of transition: Eörs Szathmary, Collegium Budapest
* Conceptual differences in the two syntheses: Alan Love, University of Minnesota

It looks pretty interesting. Some, but not all, of these topics need to be incorporated into modern evolutionary theory. It's too bad they're missing some other topics that should be there (group selection, species sorting, speciation). This conference would be much better if Stephen Jay Gould were still alive and could attend.

---

Speaking of cheating ....

 
The Face book controversy [Is it cheating to discuss an assignment in a Facebook study group?] has spread to lots of other blogs. On some of them, support for the students is getting bloggers in all kinds of hot water (e.g., A Blog Around the Clock).

Meanwhile, PZ Myers exposes another kind of cheating. This time it's the Intelligent Design Creationists () who are caught with their pants down. Read how Casey Luskin completely misrepresents the National Academy of Sciences with some very creative quote mining [Why do newspapers continue to publish Discovery Institute press releases?].

This is clearly dishonest behavior and it's about time for the general public to take notice. It will be interesting to see if any Intelligent Design Creationist tries to distance themselves from Casey Luskin. It would be a shock if any of them actually criticize Luskin for his dishonesty. If you know of a single example of a honest Intelligent Design Creationist who admits that Luskin was dishonest then please let me know. I'd like to praise them in a separate posting. Let's see if Denyse O'Leary, Bill Dembski or Micheal Behe can step up to the plate.

---

Happy Birthday PZ Myers

 

Today is PZ's 51st birthday. Here's a photo¹ of him sitting in the cafeteria of the Natural History Museum in London.

That's a famous guy sitting next to him but PZ doesn't seem to have noticed.

Bora is collecting all the birthday postings here.

---

1. The photo is a bit grainy because my camera was on movie mode. Trust me, you don't want to see the complete movie.

Paris Slideshow

 
Here are some picture from Paris. I'm experimenting with slideshows.




Paris Slideshow

---