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PMID: 11782529 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Blocking site-to-site translocation of a misactivated amino acid by mutation of a class I tRNA synthetase.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 99 ·No. 2 ·2002-01-22 ·Pages 585-90

Bishop AC, Nomanbhoy TK, Schimmel P

Abstract

The genetic code is established by the aminoacylation reactions of tRNA synthetases. Its accuracy depends on editing reactions that prevent amino acids from being assigned to incorrect codons. A group of class I synthetases share a common insertion that encodes a distinct site for editing that is about 30 A from the active site. Both misactivated aminoacyl adenylates and mischarged amino acids attached to tRNA are translocated to this site, which, in turn, is divided into subsites--one for the adenylate and one for the aminoacyl moiety attached to tRNA. Here we report that a specific mutation in isoleucyl-tRNA synthetase prevents editing by blocking translocation. The mutation alters a widely conserved residue that is believed to tether the amino group of mischarged tRNA to its subsite for editing. These and other data support a model where editing is initiated by translocation of the misacylated amino acid attached to tRNA to create an "editing complex" that facilitates subsequent rounds of editing by translocation of the misactivated adenylate.

MeSH Terms
Amino Acid Sequence Binding Sites/genetics Biological Transport, Active/genetics Isoleucine-tRNA Ligase/chemistry,genetics,metabolism Models, Biological Models, Molecular Molecular Sequence Data Mutagenesis, Site-Directed Protein Conformation RNA Editing RNA, Transfer, Ile/metabolism Sequence Homology, Amino Acid Thermus thermophilus/enzymology,genetics
Chemicals
RNA, Transfer, Ile Isoleucine-tRNA Ligase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bishop Anthony C
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, Beckman Center, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Nomanbhoy Tyzoon K
Schimmel Paul
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.012611299
Published
2002-01-22
Epub
2002-00-08
Pages
585-90
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC117349
Subset
IM
Grants
NIGMS NIH HHS · R01 GM015539 · United States
NIGMS NIH HHS · GM15539 · United States
External Links
PubMed source DOI: 10.1073/pnas.012611299 PMC Full Text View journal details
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