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Structural insights into RNA-dependent eukaryal and archaeal selenocysteine formation

Journal Article · · Nucleic Acids Research
DOI:https://doi.org/10.1093/nar/gkm1122· OSTI ID:1625420
 [1];  [2];  [3];  [2];  [2];  [2];  [3];  [4];  [2];  [2];  [5]
  1. Tokyo Institute of Technology (Japan). Graduate SChool of Bioscience and Biotechnology. Dept. of Biological Information; DOE/OSTI
  2. Yale Univ., New Haven, CT (United States). Dept. of Molecular Biophysics and Biochemistry
  3. Tokyo Institute of Technology (Japan). Graduate SChool of Bioscience and Biotechnology. Dept. of Biological Information
  4. RIKEN, Saitama (Japan). Biomolecular Characterization
  5. Tokyo Institute of Technology (Japan). Graduate SChool of Bioscience and Biotechnology. Dept. of Biological Information; SORST, Saitama (Japan). JST
The micronutrient selenium is present in proteins as selenocysteine (Sec). In eukaryotes and archaea, Sec is formed in a tRNA-dependent conversion of O-phosphoserine (Sep) by O-phosphoseryltRNA:selenocysteinyl-tRNA synthase (SepSecS). Here, we present the crystal structure of Methanococcus maripaludis SepSecS complexed with PLP at 2.5 Å resolution. SepSecS, a member of the Fold Type I PLP enzyme family, forms an (a2)2 homotetramer through its N-terminal extension. The active site lies on the dimer interface with each monomer contributing essential residues. In contrast to other Fold Type I PLP enzymes, Asn247 in SepSecS replaces the conserved Asp in binding the pyridinium nitrogen of PLP. A structural comparison with Escherichia coli selenocysteine lyase allowed construction of a model of Sep binding to the SepSecS catalytic site. Mutations of three conserved active site arginines (Arg72, Arg94, Arg307), protruding from the neighboring subunit, led to loss of in vivo and in vitro activity. The lack of active site cysteines demonstrates that a perselenide is not involved in SepSecS-catalyzed Sec formation; instead, the conserved arginines may facilitate the selenation reaction. Structural phylogeny shows that SepSecS evolved early in the history of PLP enzymes, and indicates that tRNA-dependent Sec formation is a primordial process.
Research Organization:
Yale Univ., New Haven, CT (United States)
Sponsoring Organization:
Japan Society for the Promotion of Science (JSPS); National Institutes of Health (NIH); National Science Foundation (NSF); USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division
OSTI ID:
1625420
Journal Information:
Nucleic Acids Research, Journal Name: Nucleic Acids Research Journal Issue: 4 Vol. 36; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English

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Cited By (11)

Structural basis for early-onset neurological disorders caused by mutations in human selenocysteine synthase journal August 2016
From one amino acid to another: tRNA-dependent amino acid biosynthesis journal February 2008
Prognostic Implications of Antibodies to Soluble Liver Antigen in Autoimmune Hepatitis journal June 2015
Selenocysteine, Pyrrolysine, and the Unique Energy Metabolism of Methanogenic Archaea journal January 2010
Structural mimicry between SLA/LP and Rickettsia surface antigens as a driver of autoimmune hepatitis: insights from an in silico study journal April 2013
Crystal Structure Analysis Reveals Functional Flexibility in the Selenocysteine-Specific tRNA from Mouse journal May 2011
Selenium-Dependent Antioxidant Enzymes: Actions and Properties of Selenoproteins journal May 2018
Challenges of site-specific selenocysteine incorporation into proteins by Escherichia coli journal November 2017
Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase posted_content January 2020
Genetic analysis of selenocysteine biosynthesis in the archaeon Methanococcus maripaludis journal May 2011
Trypanosomatid selenophosphate synthetase structure, function and interaction with selenocysteine lyase journal October 2020

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