A Minimal TrpRS Catalytic Domain Supports Sense/Antisense Ancestry of Class I and II Aminoacyl-tRNA Synthetases

Yen Pham, Li Li, Aram Kim, Ozgun Erdogan, Violetta Weinreb, Glenn L. Butterfoss, Brian Kuhlman, Charles W. Carter

Research output: Contribution to journalArticle

Abstract

The emergence of polypeptide catalysts for amino acid activation, the slowest step in protein synthesis, poses a significant puzzle associated with the origin of biology. This problem is compounded as the 20 contemporary aminoacyl-tRNA synthetases belong to two quite distinct families. We describe here the use of protein design to show experimentally that a minimal class I aminoacyl-tRNA synthetase active site might have functioned in the distant past. We deleted the anticodon binding domain from tryptophanyl-tRNA synthetase and fused the discontinuous segments comprising its active site. The resulting 130 residue minimal catalytic domain activates tryptophan. This residual catalytic activity constitutes the first experimental evidence that the conserved class I signature sequences, HIGH and KMSKS, might have arisen in-frame, opposite motifs 2 and 1 from class II, as complementary sense and antisense strands of the same ancestral gene.

Original languageEnglish (US)
Pages (from-to)851-862
Number of pages12
JournalMolecular Cell
Volume25
Issue number6
DOIs
StatePublished - Mar 23 2007

Keywords

  • RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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