The α Helix

 
Monday's molecule #63 is an α helix. This conformation of amino acids was first discovered by Linus Pauling who received the Nobel Prize in 1954, partly for his work on the α helix.

The following description of the α helix is taken from Horton et al. (2006) Principles of Biochemistry.

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Figure 4.10
α Helix. A region of α-helical secondary structure is shown with the N-terminus at the bottom and the C-terminus at the top of the figure. Each carbonyl oxygen forms a hydrogen bond with the amide hydrogen of the fourth residue further toward the C-terminus of the polypeptide chain. The hydrogen bonds are approximately parallel to the long axis of the helix. Note that all the carbonyl groups point toward the C-terminus. In an ideal α helix, equivalent positions recur every 0.54 nm (the pitch of the helix), each amino acid residue advances the helix by 0.15 nm along the long axis of the helix (the rise), and there are 3.6 amino acid residues per turn. In a right-handed helix, the backbone turns in a clockwise direction when viewed along the axis from its N-terminus. If you imagine that the right-handed helix is a spiral staircase, you will be turning to the right as you walk down the staircase.

The α-helical conformation was proposed in 1950 by Linus Pauling and Robert Corey. They considered the dimensions of peptide groups, possible steric constraints, and opportunities for stabilization by formation of hydrogen bonds. Their model accounted for the major repeat observed in the structure of the fibrous protein α-keratin. This repeat of 0.50 to 0.55 nm turned out to be the pitch (the axial distance per turn) of the α helix. Max Perutz added additional support for the structure when he observed a secondary repeating unit of 0.15 nm in the X-ray diffraction pattern of α-keratin. The 0.15 nm repeat corresponds to the rise of the helix (the distance each residue advances the helix along its axis). Perutz also showed that the α helix was present in hemoglobin, confirming that this conformation was present in more complex globular proteins.

In theory, an α helix can be either a right- or a left-handed screw. The α helices found in proteins are almost always right-handed, as shown in Figure 4.10. In an ideal α helix, the pitch is 0.54 nm, the rise is 0.15 nm, and the number of amino acid residues required for one complete turn is 3.6 (i.e., approximately 3 2/3 residues:one carbonyl group, three N—Cα—C units, and one nitrogen). Most α helices are slightly distorted in proteins but they generally have between 3.5 and 3.7 residues per turn.

Within an α helix, each carbonyl oxygen (residue n) of the polypeptide backbone is hydrogen-bonded to the backbone amide hydrogen of the fourth residue further toward the C-terminus (residue n + 4). (The three amino groups at one end of the helix and the three carbonyl groups at the other end lack hydrogenbonding partners within the helix.) Each hydrogen bond closes a loop containing 13 atoms—the carbonyl oxygen, 11 backbone atoms, and the amide hydrogen. This α helix can also be called a 3.6₁₃ helix, based on its pitch and hydrogen-bonded loop size. The hydrogen bonds that stabilize the helix are nearly parallel to the long axis of the helix.

Figure 4.11
View of a right-handed α helix. The blue ribbon indicates the shape of the polypeptide backbone. All the side chains, shown as ball-and-stick models, project outward from the helix axis. This example is from residues Ile-355 (bottom) to Gly-365 (top) of horse liver alcohol dehydrogenase. Some hydrogen atoms are not shown. [PDB 1ADF].

A single intrahelical hydrogen bond would not provide appreciable structural stability but the cumulative effect of many hydrogen bonds within an α helix stabilizes this conformation. Hydrogen bonds between amino acid residues are especially stable in the hydrophobic interior of a protein where water molecules do not enter and therefore cannot compete for hydrogen bonding. In an α helix, all the carbonyl groups point toward the C-terminus. Since each peptide group is polar and all the hydrogen bonds point in the same direction, the entire helix is a dipole with a positive N-terminus and a negative C-terminus.

The side chains of the amino acids in an α helix point outward from the cylinder of the helix (Figure 4.11). The stability of an helix is affected by the identity of the side chains. Some amino acid residues are found in conformations more often than others. For example, alanine has a small, uncharged side chain and fits well into the α-helical conformation. Alanine residues are prevalent in the α helices of all classes of proteins. In contrast, tyrosine and asparagine with their bulky side chains are less common in α helices. Glycine, whose side chain is a single hydrogen atom, destabilizes α-helical structures since rotation around its α-carbon is so unconstrained. For this reason, many helices begin or end with glycine residues. Proline is the least common residue in an α helix because its rigid cyclic side chain disrupts the right-handed helical conformation by occupying space that a neighboring residue of the helix would otherwise occupy. In addition, because it lacks a hydrogen atom on its amide nitrogen, proline cannot fully participate in intrahelical hydrogen bonding. For these reasons, proline residues are found more often at the ends of α helices than in the interior.

Proteins vary in their α-helical content. In some, most of the residues are in helices. Other proteins contain very little structure. The average content of helix in the proteins that have been examined is 26%. The length of a helix in a protein can range from about 4 or 5 residues to more than 40, but the average is about 12.

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©Laurence A. Moran and Pearson Prentice Hall

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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)