title: Complete pathway for protein disulfide bond formation encoded by poxviruses.
abstract: We show that three cytoplasmic thiol oxidoreductases encoded by vaccinia virus comprise a complete pathway for formation of disulfide bonds in intracellular virion membrane proteins. The pathway was defined by analyzing conditional lethal mutants and effects of cysteine to serine substitutions and by trapping disulfide-bonded heterodimer intermediates for each consecutive step. The upstream component, E10R, belongs to the ERV1/ALR family of FAD-containing sulfhydryl oxidases that use oxygen as the electron acceptor. The second component, A2.5L, is a small alpha-helical protein with a CxxxC motif that forms a stable disulfide-linked heterodimer with E10R and a transient disulfide-linked complex with the third component, G4L. The latter is a thioredoxin-like protein that directly oxidizes thiols of L1R, a structural component of the virion membrane with three stable disulfide bonds, and of the related protein F9L. These five proteins are conserved in all poxviruses, suggesting that the pathway is an ancestral mechanism for direct thiol-disulfide interchanges between proteins even in an unfavorable reducing environment.
authors: Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Tatiana G
authors: TG
authors: Senkevich
authors: Christine L
authors: CL
authors: White
authors: Eugene V
authors: EV
authors: Koonin
authors: Bernard
authors: B
authors: Moss
mesh_terms: D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D003545:Cysteine; D019281:Dimerization; D004220:Disulfides; D011490:Protein Disulfide Reductase (Glutathione) / Q000235:genetics / Q000378:metabolism*; D012694:Serine; D014616:Vaccinia virus / Q000201:enzymology* / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D004220:Disulfides; C087715:L1R protein, Vaccinia virus; D014759:Viral Envelope Proteins; D012694:Serine; D011490:Protein Disulfide Reductase (Glutathione); D003545:Cysteine