A novel cysteine-rich domain of Sep15 mediates the interaction with UDP-glucose:glycoprotein glucosyltransferase

Vyacheslav M. Labunskyy, Andrew D. Ferguson, Dmitri E. Fomenko, Yogarany Chelliah, Dolph L. Hatfield, Vadim N. Gladyshev

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Selenium is an essential trace element with potent cancer prevention activity in mammals. The 15-kDa selenoprotein (Sep15) has been implicated in the chemopreventive effect of dietary selenium. Although the precise function of Sep15 remains elusive, Sep15 co-purifies with UDP-glucose:glycoprotein glucosyltransferase (GT), an essential regulator of quality control mechanisms within the endoplasmic reticulum. Recent studies identified two GT and two Sep15 homologues in mammals. We characterize interactions between these protein families in this report. Sep15 and GT form a tight 1:1 complex, and these interactions are conserved between mammals and fruit flies. In mammalian cells, Sep15 co-immunoprecipitates with both GT isozymes. In contrast, a Sep15 homologue, designated selenoprotein M (SelM), does not form a complex with GT. Sequence analysis of members of the Sep15 family identified a novel N-terminal cysteine-rich domain in SeplS that is absent in SelM. This domain contains six conserved cysteine residues that form two CxxC motifs that do not coordinate metal ions. If this domain is deleted or the cysteines are mutated, Sep15 no longer forms a complex with GT. Conversely, if the cysteine-rich domain of Sep15 is fused to the N-terminus of SelM, the resulting chimera is capable of binding GT. These data indicate that the cysteine-rich domain of Sep15 exclusively mediates protein-protein interactions with GT.

Original languageEnglish (US)
Pages (from-to)37839-37845
Number of pages7
JournalJournal of Biological Chemistry
Volume280
Issue number45
DOIs
StatePublished - Nov 11 2005

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Glucosyltransferases
Cysteine
Selenoproteins
Mammals
Selenium
Proteins
Trace Elements
Fruits
mannosylglycoprotein 1,3-glucosyltransferase
Diptera
Endoplasmic Reticulum
Quality Control
Isoenzymes
Quality control
Metal ions
Sequence Analysis
Fruit
Metals
Cells
Ions

ASJC Scopus subject areas

  • Biochemistry

Cite this

A novel cysteine-rich domain of Sep15 mediates the interaction with UDP-glucose:glycoprotein glucosyltransferase. / Labunskyy, Vyacheslav M.; Ferguson, Andrew D.; Fomenko, Dmitri E.; Chelliah, Yogarany; Hatfield, Dolph L.; Gladyshev, Vadim N.

In: Journal of Biological Chemistry, Vol. 280, No. 45, 11.11.2005, p. 37839-37845.

Research output: Contribution to journalArticle

Labunskyy, Vyacheslav M. ; Ferguson, Andrew D. ; Fomenko, Dmitri E. ; Chelliah, Yogarany ; Hatfield, Dolph L. ; Gladyshev, Vadim N. / A novel cysteine-rich domain of Sep15 mediates the interaction with UDP-glucose:glycoprotein glucosyltransferase. In: Journal of Biological Chemistry. 2005 ; Vol. 280, No. 45. pp. 37839-37845.
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