Mutational unmasking of a tRNA-dependent pathway for preventing genetic code ambiguity

Proceedings of the National Academy of Sciences of the United States of America
Amy M Williams, Susan A Martinis

Abstract

Aminoacyl-tRNA synthetases establish the genetic code by matching each amino acid with its cognate tRNA. Aminoacylation errors lead to genetic code ambiguity and statistical proteins. Some synthetases have editing activities that clear the wrong amino acid (aa) by hydrolysis of either of two substrates: misactivated aminoacyl-adenylates ("pretransfer" of aa to tRNA) or misacylated aa-tRNA ("posttransfer"). Whereas posttransfer editing can be directly measured, pretransfer editing is difficult to demonstrate, because adenylates are inherently labile and transient, and activity occurs against a background of posttransfer editing. Herein, different mutations in Escherichia coli leucyl-tRNA synthetase are combined to unmask the pretransfer pathway. The mutant enzymes completely lack posttransfer editing but prevent misacylations by clearing misactivated adenylates. We hypothesize that these mutations isolate a pretransfer translocation step that moves misactivated adenylates from the activation site for editing. The results highlight how evolution redundantly created two distinct pathways to prevent genetic code ambiguity.

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Citations

Oct 25, 2011·Journal of the American Chemical Society·Jaya Sarkar, Susan A Martinis
Aug 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sang Gyu ParkSunghoon Kim
Oct 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Benfang RuanDieter Söll
Nov 21, 2008·Proceedings of the National Academy of Sciences of the United States of America·Michal T BonieckiSusan A Martinis
Dec 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Srujana S YadavalliMichael Ibba
Feb 4, 2009·The Journal of Biological Chemistry·Kristina Mary Ellen WeimerSanchita Hati
Apr 22, 2009·Annual Review of Microbiology·Jiqiang LingMichael Ibba
Nov 28, 2009·FEBS Letters·Susan A Martinis, Michal T Boniecki
Apr 8, 2014·Wiley Interdisciplinary Reviews. RNA·Yan Ling Joy PangSusan A Martinis
Jun 5, 2008·FEMS Microbiology Reviews·Corinne D Hausmann, Michael Ibba
Dec 14, 2006·ACS Chemical Biology·Sandro F Ataide, Michael Ibba
Nov 1, 2012·EcoSal Plus·Richard Giegé, Mathias Springer
Feb 5, 2008·Methods : a Companion to Methods in Enzymology·Kathryn E SplanSusan A Martinis

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