AsianScientist (Jun 16, 2014) – In work published in Nature, scientists from RIKEN, along with colleagues from the University of Tokyo, have identified a surprising mechanism that allows the enzyme alanyl-tRNA synthetase to properly assemble a tRNA molecule with its cognate amino acid, shedding light on the basis of the accurate translation of the genetic code into proteins.
The translation of genetic information into proteins depends upon a precise process whereby molecules called transfer RNA (tRNA) bind to specific amino acids. Mistakes in this process, which is mediated by enzymes called synthetases, can be disastrous, as they can lead to improperly formed proteins. Although tRNA molecules are matched to the proper amino acids with great precision, scientists lack a fundamental understanding of how this selection takes place.
Using crystallographic studies of molecules in a micro-organism, a group led by Professor Shigeyuki Yokoyama from RIKEN has determined that the enzyme precisely identifies the proper tRNA thanks to a unique geometric feature: the arrangement of a single base pair in the tRNA molecule that is placed in a “wobble” configuration.
The wobble base pair, between guanine at position 3 and uracil at position 70 (G3●U70), allows the tRNA for alanine but not for other amino acids to come into contact with the enzyme’s active region. By looking at a complex of alanyl-tRNA synthetase with the wild-type tRNA compared with a variant where the guanine is replaced by adenine, the researchers found that the wild type tRNA adopts a straight conformation, placing the single stranded region in the active site of the alanyl-tRNA synthetase enzyme. However, the adenine tRNA variant had a bent conformation, keeping it separated from the active region, in what Yokoyama calls a “non-reactive state”.
The configuration change in the tRNA molecule caused the reaction rate in the adenine variant to be 100 times slower than that of wild-type tRNA. This showed that the alanyl-tRNA synthetase enzyme exploits the small change in geometry to make the recognition of tRNA molecules accurate.
“This is a fascinating finding that may give us new insights into how living systems can so accurately translate their genetic code through processes that are at their core stochastic or random, using even small structural changes,” said Yokohama.
“Our work is interesting in terms of the evolution of the genetic code, since acceptor stem recognition is important for the concept of the ‘second genetic code’. The findings in this paper may show a previously unknown mechanism of tRNA recognition inherited from a distant ancestor.”
The article can be found at: Naganuma et al. (2014) The selective tRNA aminoacylation mechanism based on a single G•U pair.
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Source: RIKEN.
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