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 Citations (Scopus)

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

Fingerprint

Selenocysteine
Peptide Elongation Factors
Guanine Nucleotides
Terminator Codon
elongation
Crystal structure
Peptide Elongation Factor Tu
Selenoproteins
crystal structure
guanines
nucleotides
Guanosine Triphosphate
Eukaryota
Ribosomes
Decoding
prokaryotes
eukaryotes
ribosomes
Amino Acids
decoding

ASJC Scopus subject areas

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

Cite this

Crystal structures of the human elongation factor eEFSec suggest a non-canonical mechanism for selenocysteine incorporation. / Dobosz-Bartoszek, Malgorzata; Pinkerton, Mark H.; Otwinowski, Zbyszek; Chakravarthy, Srinivas; Söll, Dieter; Copeland, Paul R.; Simonovic, Miljan.

In: Nature Communications, Vol. 7, 12941, 06.10.2016.

Research output: Contribution to journalArticle

Dobosz-Bartoszek, Malgorzata ; Pinkerton, Mark H. ; Otwinowski, Zbyszek ; Chakravarthy, Srinivas ; Söll, Dieter ; Copeland, Paul R. ; Simonovic, Miljan. / Crystal structures of the human elongation factor eEFSec suggest a non-canonical mechanism for selenocysteine incorporation. In: Nature Communications. 2016 ; Vol. 7.
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AU - Copeland, Paul R.

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