Structural and mechanistic basis of pre- and posttransfer editing by leucyl-tRNA synthetase

Tommie L. Lincecum, Michael Tukalo, Anna Yaremchuk, Richard S. Mursinna, Amy M. Williams, Brian S. Sproat, Wendy Van Den Eynde, Andreas Link, Serge Van Calenbergh, Morten Grøtli, Susan A. Martinis, Stephen Cusack

Research output: Contribution to journalArticlepeer-review

Abstract

The aminoacyl-tRNA synthetases link tRNAs with their cognate amino acid. In some cases, their fidelity relies on hydrolytic editing that destroys incorrectly activated amino acids or mischarged tRNAs. We present structures of leucyl-tRNA synthetase complexed with analogs of the distinct pre- and posttransfer editing substrates. The editing active site binds the two different substrates using a single amino acid discriminatory pocket while preserving the same mode of adenine recognition. This suggests a similar mechanism of hydrolysis for both editing substrates that depends on a key, completely conserved aspartic acid, which interacts with the α-amino group of the noncognate amino acid and positions both substrates for hydrolysis. Our results demonstrate the economy by which a single active site accommodates two distinct substrates in a proofreading process critical to the fidelity of protein synthesis.

Original languageEnglish (US)
Pages (from-to)951-963
Number of pages13
JournalMolecular cell
Volume11
Issue number4
DOIs
StatePublished - Apr 1 2003

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Structural and mechanistic basis of pre- and posttransfer editing by leucyl-tRNA synthetase'. Together they form a unique fingerprint.

Cite this