Wednesday, October 7, 2009


The 2009 Nobel Prize in Chemistry was awarded to Venkatraman Ramakrishnan, Thomas Steitz, and Ada Yonath for their elucidation of the structure of ribosomes and how that structure promotes accurate translation of messenger RNA sequences into the amino acid sequences of proteins.

Ribosomes are the granddaddies of the ribonucleoprotein machines in the cell--big enough to be customarily granted organelle status even though they don't have a membrane. The bacterial version of the complex, for example consists of two large parts, denoted 30S and 50S to represent how fast they separate out of a suspension. Each of these subunits contains many proteins (20 and 33, respectively), together with large "ribosomal" RNA chains.

With the assistance of transfer RNA, ribosomes translate messenger RNA sequences (previously transcribed from DNA in the nucleus) into a corresponding amino-acid sequence or polypeptide, which will be folded and processed into a mature, functioning protein. In light of this critical and intricate task, it should probably not be surprising that the ribosome is very similar in widely different species. However, bacterial, archaeal, and eukaryotic ribosomes are rather different, and the differences in the ribosomal RNA were used by Carl Woese in the 1970s as the evidence for the highest-level classifying of life forms into these three broad domains.

Streptomycin, tetracycline, and about half of current antibiotics preferentially disrupt bacterial protein synthesis by attacking the bacteria-specific versions of the ribosome. The details of the ribosome structure can guide researchers who hope to develop new types of antibiotic molecules.

The three researchers and their collaborators all studied the structure of ribosomes by x-ray crystallography. This structure revealed specific details about how transfer RNA, with its individual matching amino acid cargo, nestles into the ribosome, and how the amino acid forms a covalent bond with the growing polypeptide. (The Nobel Committee notes that the charge-coupled devices that garnered this year's physics prize have made such studies much more productive.) Researchers have used these and other studies to clarify the entropy and energy that drives this synthesis.

A critical aspect of quality control in protein synthesis is the "proofreading" that ensures that the RNA sequence in the transfer RNA is indeed complementary to that of the messenger RNA. In 1974, John Hopfield (then at Princeton and Bell Labs) proposed that a multi-step ratchet that repeatedly checks the match while expending energy could be more selective than depending on the rather weak thermodynamic preference for a match. The increasingly refined structures revealed by the prize winners, together with other experiments, have confirmed how this proofreading works in the real ribosome, achieving an amazingly low error rate of about one error in 10,000 amino acids.

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