A flavoprotein oxidase defines a new endoplasmic reticulum pathway for biosynthetic disulphide bond formation.
Ero1 and Pdi1 are essential elements of the pathway for the formation of disulphide bonds within the endoplasmic reticulum (ER). By screening for alternative oxidation pathways in Saccharomyces cerevisiae, we identified ERV2 as a gene that when overexpressed can restore viability and disulphide bond formation to an ero1-1 mutant strain. ERV2 encodes a luminal ER protein of relative molecular mass 22,000. Purified recombinant Erv2p is a flavoenzyme that can catalyse O2-dependent formation of disulphide bonds. Erv2p transfers oxidizing equivalents to Pdi1p by a dithiol-disulphide exchange reaction, indicating that the Erv2p-dependent pathway for disulphide bond formation closely parallels that of the previously identified Ero1p-dependent pathway.
Sevier
C S
CS
Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA.
Cuozzo
J W
JW
Vala
A
A
Aslund
F
F
Kaiser
C A
CA
D000595:Amino Acid Sequence; D004220:Disulfides / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000201:enzymology*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010088:Oxidoreductases; D019704:Protein Disulfide-Isomerases; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment
D004220:Disulfides; D005656:Fungal Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; C080576:PDI1 protein, S cerevisiae; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D010088:Oxidoreductases; C111280:ERV2 protein, S cerevisiae; D019704:Protein Disulfide-Isomerases