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SUMMARY:Accuracy of codon reading by transfer RNAs - Måns Ehrenberg
DTSTART:20110218T113000Z
DTEND:20110218T131500Z
UID:TALK29933@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Translation of the genetic code on ribosomes requires recognit
 ion of 61 sense codons by amino acid carrying transfer RNAs. mRNA translat
 ion has evolved to high speed and high accuracy. The accuracy of sense cod
 on reading relies on Watson-Crick base pairing between the three codon bas
 es of mRNA and the three anticodon bases of tRNAs cognate to the codons\, 
 but also on ribosome aided stereo-selection of the codon-anticodon helix. 
 The accuracy of tRNA recognition is greatly enhanced by a two-step mechani
 sm\, consisting of initial selection and proofreading selection\, where th
 e two steps are separated by GTP-hydrolysis on elongation factor Tu in ter
 nary complex with tRNA and GTP. This separation of steps by a large chemic
 al potential decrease allows for repeated selection of the very same stand
 ard free energy difference between cognate and non-cognate codon-anticodon
  interactions at transition states for GTP-hydrolysis (initial selection) 
 and aa-tRNA accommodation and peptidyl transfer (proofreading selection). 
 \nStructural elements of codon-anticodon interactions of importance for th
 e accuracy of genetic code translation define the intrinsic single step se
 lectivity of codon reading (d-value)\, the actual (current) selectivity of
  single step reading (I-value for initial and F-value for proofreading). W
 e will discuss the speed-accuracy trade-off of single step codon reading: 
 when the I- or F-value approaches the d-value the rate of codon translatio
 n necessarily goes to zero. The working principle of proofreading and its 
 manifestation in codon translation will be discussed along with a novel ty
 pe of biochemical experiments to estimate I- and F-values as well as intri
 nsic d-values: the rate-accuracy trade off leads to linear plots\, from wh
 ich the d-values of discrimination against near-cognate codons by Lys-tRNA
 Lys in ternary complex with EF-Tu and GTP. It seems that this method can b
 e generalized to all aminoacyl-tRNAs and all ribosomal contexts\, as deter
 mined by mutations\, modification deficiencies\, drugs etc. Calibration of
  biochemical systems to the accuracy of codon reading in the living cell w
 ill be discussed along with criteria for optimal translation accuracy for 
 maximal fitness of growing cells. \n\n
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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