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Thursday, March 15, 2012

What Does a Eukaryotic Ribosome Look Like?

There's a picture of a yeast (Saccharomyces cerevisiae) ribosome on the cover of the Dec. 16, 2011 issue of Science. The paper inside by Ben-Sham et al. (2011) describes the structure at 3Å resolution.

There's nothing revolutionary here but I thought I would show you the structure just to emphasize a particular point. You can see the same image below without the distracting orange background.

Most of the ribosome is composed of RNA (silver-gray strands). You can see that a lot of this single-stranded RNA forms short double-helical regions when the RNA folds back on itself. Small ribosomal proteins (various colors) decorate the surface of the ribosome by binding to specific regions of the ribosomal RNA.

The overall impression is that the ribosome is a big ball of RNA with a small amount of protein. The actual site of translation, where messenger RNA is translated into a polypeptide, takes place in the middle of the ribosome near the hole you see in this structure. Translation is catalzyed by the RNA component of the ribosome, not by the ribosomal proteins.

I don't know about the rest of you but I grew up with an electron-micrographic image of a ribosome in my head and I just assumed that what I was seeing was a large glob of protein. If course I realized that there was a huge amount or RNA in there somewhere but I didn't think it contributed very much to the dark blobs in the cell.

When the first crystal structures of ribosomes were published I had to stare at them for quite some time in order to purge the old images from my mind and adopt a new perspective.

Eukaryotes have 79 ribosomal proteins and prokaryotic ribosomes have only 52 proteins. There are prokaryotic ribosomal proteins that have no homoogues in eukaryotes and 33 of the eukaryotic ribosomal proteins have no homologues in bacteria—they are eukaryotic specific. Furthermore, many of the eukaryotic proteins differ considerably from their bacterial homologues. (Mostly by extensions of the poly peptide chain.)

The protein components of ribosomes are not highly conserved. One gets the impression that they don't contribute much to the function of a ribosome—an impression confirmed by the fact that the RNA by itself can catalyze polypeptide synthesis. They may help stabilize the three-dimensional structure of the ribosome.

[Image credit: The bottom image is "courtesy of Prof Marat Yusupov (IGBMC, Strasbourg)" from The 9th international Conference on Ribosome Synthesis that takes place this summer in Banff, Alberta, Canada.]

Ben-Shem A, Garreau de Loubresse N, Melnikov S, Jenner L, Yusupova G, Yusupov M. (2011) The structure of the eukaryotic ribosome at 3.0 Å resolution. Science 334:1524-1529. (Epub 2011 Nov 17). [doi: 10.1126/science.1212642]


TheBrummell said...

I don't know about the rest of you but I grew up with an electron-micrographic image of a ribosome in my head and I just assumed that what I was seeing was a large glob of protein.

I can't remember the first time I was introduced to a ribosome - certainly there were small dark-blue spheres in the diagrams of cells in my high school biology textbooks, but an in-depth discussion of them probably didn't happen until sometime during my B.Sc. I can't recall ever thinking of them as primarily protein, I must have been introduced to them via discussions of the different types of RNA found in cells. I think of nucleic acids as strings, so the electron micrographs of ribosomes I saw immediately looked like tangled balls of string to me.

I'm actually mildly suprised at the amount of protein shown in the illustration - I'd always mentally dismissed the protein component of ribosomes as insignificant, since it was known (or, at least explained to me with a bit of an air of authority) that RNA participated directly in the formation of polypeptides.

Andy Pierce said...

There are human diseases associated with dysfunctional (haploinsufficient) ribosomal proteins such as Diamond-Blackfan anemia. There is also an interesting "spotty belly, twisty tail" mouse phenotype associated with defects in ribosomal proteins. I don't know of any human diseases associated with either not enough copies of rRNA or defective copies of rRNA. It was my suspicion given the large variability in rRNA copy number in humans that too few copies of rRNA genes would also cause Diamond-Blackfan anemia. Unfortunately, the NIH study section didn't see the wisdom in funding this grant proposal...

Anonymous said...

"an impression confirmed by the fact that the RNA by itself can catalyze polypeptide synthesis"

Thats mind-blowing, though I cant imagine how they stabilized the RNA without any protein. Can you point me to a reference on that?
I was thinking it would be interesting to remove a selected protein from a ribosome and then randomly mutate the RNA to restore function. If it worked it would be a nice, easy-to-discuss refutation of IC - problem is, scientists never work soley to discredit creationists.

Anonymous said...

I wouldn't wanna be the designer of that crazy ass thing!

Reginald Selkirk said...

My own pet thought is that the proteins serve as a 'coat of armour', because one of the earliest enzymes produced by the ribosome was ribonuclease. Warfare in the RNA World.

David said...

Some people, however, still have proven impervious to such evidence. The DiscoTute has a recent post that is a gem in this regard: Start counting the errors: evidently the PTC was considered the oldest part of the ribosome protein. As I recall the same kinds of errors were common in Stephen Meyer's book a few years ago - references to the peptidyl transferase protein and a ribosome made mostly of protein. I still can't tell if they're intentionally trying to play down RNA's role in translation or remain blissfully unaware.

Marshall said...

I think that the idea of Ribosomal proteins being inert except for slight stabilizing effects on rRNA tertiary structure is also a bit behind the times. It's been quite clear for a while that most of them are required for ribosome biogenesis and localization to the nucleolus. What's even more cool (in my mind anyway, as I studied r-proteins in arabidopsis for a few years) is that even though r-proteins are not highly conserved between species, evidence is starting to trickle in that r-proteins are fundamental to a number of physiological and developmental processes. For example preferentially directing translation of patterning genes in mice or directing translation of cold-tolerance genes in tobacco.

Even cooler than that (again, I'm biased due to being a bit of a ribosome nerd) is this recent phylogenetic study of r-protein and rRNA structures that seems to suggest that ribosomal proteins and catalytic RNA have co-evolved, further indicating that r-proteins, although higly variable, have always played an important role in the function of the ribosome.

It's neat to think that some day pretty soon we'll all have to re-evaluate our conception of the ribosome as a single-function translator of mRNA into protein. Hopefully we'll learn more about how they act in the physiology of the cell.

David said...

Hmmm… Hashing this out in the comments section of an aging blog post is perhaps not the most productive approach, but I found that plos one paper you mention problematic.

First, they argue for the existence of r-Proteins before coded protein synthesis. So at some point in the past r-Proteins were not encoded in nucleic acids, but in current organisms, they are. In between, information had to flow from protein sequence into nucleic acid, i.e. reverse translation. No such process can be found in biology, and there are good biochemical reasons to suspect it would be prohibitively difficult. And yet they never even consider this issue in their conclusions.

Separately (and I would sincerely appreciate the comments of anybody more familiar with the relevant phylogenetics literature), their phylogenetic reconstruction of ribosomal history is very odd. This is not a standard phylogenetic tree: the leaves of the tree are not ribosomes sharing a common ribosomal ancestor. Instead they’re generating a tree of helices, which seems to suggest that all the helices in the modern ribosome are related by common ancestry… an odd claim.

Relatedly, they are using variation in modern, extant ribosomes to reconstruct the origin of universal elements of ribosomal structure– that is they’re using variation that arose post-divergence from the LUCA of ribosomes to reconstruct evolution of the ribosome _before_ that divergence. This seems… implausible. I would be more convinced if they could point to anyone other than themselves who have used these methods, or even an extensive justification of why these methods should work.