A 4-Selenocysteine, 2-Selenocysteine Insertion Sequence (SECIS) Element Methionine Sulfoxide Reductase from Metridium senile Reveals a Non-catalytic Function of Selenocysteines

Authors

Byung Cheon Lee, Brigham and Women’s Hospital and Harvard Medical SchoolFollow
Alexey V. Lobanov, University of Nebraska - LincolnFollow
Stefano M. Marino, University of Nebraska-LincolnFollow
Alaattin Kaya, Brigham and Women’s Hospital and Harvard Medical School
Javier Seravalli, University of Nebraska-LincolnFollow
Dolph L. Hatfield, National Institutes of Health, Bethesda, MDFollow
Vadim N. Gladyshev, Harvard Medical SchoolFollow

Date of this Version

2011

Citation

THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 286, NO. 21, pp. 18747–18755, May 27, 2011

Comments

US government work

Abstract

Selenocysteine (Sec) residues occur in thiol oxidoreductase families, and functionally characterized selenoenzymes typically have a single Sec residue used directly for redox catalysis. However, how new Sec residues evolve and whether non-catalytic Sec residues exist in proteins is not known. Here, we computationally identified several genes with multiple Sec insertion sequence (SECIS) elements, one of which was a methionine-Rsulfoxide reductase (MsrB) homolog from Metridium senile that has four in-frame UGA codons and two nearly identical SECIS elements. One of the UGA codons corresponded to the conserved catalytic Sec or Cys in MsrBs, whereas the three other UGA codons evolved recently and had no homologs with Sec or Cys in these positions. Metabolic ⁷⁵Se labeling showed that all four in-frame UGA codons supported Sec insertion and that both SECIS elements were functional and collaborated in Sec insertion at each UGA codon. Interestingly, recombinant M. senile MsrB bound iron, and further analyses suggested the possibility of binding an iron-sulfur cluster by the protein. These data show that Sec residues may appear transiently in genes containing SECIS elements and be adapted for non-catalytic functions.