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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 Simonović
Nature communications | 2016

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.

Pubmed ID: 27708257

Research resources used in this publication

None found

Antibodies used in this publication

None found

Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R24 GM115586
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM070773
  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR001863
  • Agency: NIGMS NIH HHS, United States
    Id: P41 GM103622
  • Agency: NIGMS NIH HHS, United States
    Id: R37 GM022854
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM053163
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM022854
  • Agency: NIH HHS, United States
    Id: S10 OD018090
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM117080
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM077073
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM097042

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