title: Energetic tuning by tRNA modifications ensures correct decoding of isoleucine and methionine on the ribosome.
abstract: Chemical modifications of tRNAs are critical for accurate translation of the genetic code on the ribosome. The discrimination between isoleucine (AUA) and methionine (AUG) codons depends on such modifications of the wobble position in isoleucine tRNA anticodon loops, in all kingdoms of life. Bacteria and archaea employ functionally similar lysine- and agmatine-conjugated cytidine derivatives to ensure decoding fidelity, but the thermodynamics underlying codon discrimination remains unknown. Here, we report structure-based computer simulations that quantitatively reveal the energetics of this decoding strategy in archaea. The results further show that the agmatidine modification confers tRNA specificity primarily by desolvation of the incorrect codon in the non-cognate complex. Tautomerism is found to play no significant role in this decoding system as the usual amino form of the modified tRNA is by far the most stable.
authors.affiliation: Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE-751 24 Uppsala (Sweden) http://www.icm.uu.se/research/csb/aqvist/
authors.forename: Priyadarshi
authors.initials: P
authors.lastname: Satpati
authors.forename: Paul
authors.initials: P
authors.lastname: Bauer
authors.forename: Johan
authors.initials: J
authors.lastname: Aqvist
mesh_terms: D001105:Archaea / Q000737:chemistry / Q000235:genetics*; D003062:Codon; D003562:Cytidine / Q000031:analogs & derivatives / Q000235:genetics; D007532:Isoleucine / Q000235:genetics*; D008715:Methionine / Q000235:genetics*; D056004:Molecular Dynamics Simulation; D012343:RNA, Transfer / Q000737:chemistry / Q000235:genetics*; D012270:Ribosomes / Q000235:genetics*; D013816:Thermodynamics
chemical_list: D003062:Codon; C548874:agmatidine; D007532:Isoleucine; D003562:Cytidine; D012343:RNA, Transfer; D008715:Methionine
keywords: codon reading; molecular dynamics; ribosomes; tRNA modification