Crystal structures of the human elongation factor eEFSec suggest a non-canonical mechanism for selenocysteine incorporation

Malgorzata Dobosz-Bartoszek, Mark H. Pinkerton, Zbyszek Otwinowski, Srinivas Chakravarthy, Dieter Söll, Paul R. Copeland, Miljan Simonovic

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Selenocysteine is the only proteinogenic amino acid encoded by a recoded in-frame UGA codon that does not operate as the canonical opal stop codon. A specialized translation elongation factor, eEFSec in eukaryotes and SelB in prokaryotes, promotes selenocysteine incorporation into selenoproteins by a still poorly understood mechanism. Our structural and biochemical results reveal that four domains of human eEFSec fold into a chalice-like structure that has similar binding affinities for GDP, GTP and other guanine nucleotides. Surprisingly, unlike in eEF1A and EF-Tu, the guanine nucleotide exchange does not cause a major conformational change in domain 1 of eEFSec, but instead induces a swing of domain 4. We propose that eEFSec employs a non-canonical mechanism involving the distinct C-terminal domain 4 for the release of the selenocysteinyl-tRNA during decoding on the ribosome.

Original languageEnglish (US)
Article number12941
JournalNature Communications
Volume7
DOIs
StatePublished - Oct 6 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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