Publication Date:
2000-11-25
Description:
The endoplasmic reticulum (ER) supports disulfide bond formation by a poorly understood mechanism requiring protein disulfide isomerase (PDI) and ERO1. In yeast, Ero1p-mediated oxidative folding was shown to depend on cellular flavin adenine dinucleotide (FAD) levels but not on ubiquinone or heme, and Ero1p was shown to be a FAD-binding protein. We reconstituted efficient oxidative folding in vitro using FAD, PDI, and Ero1p. Disulfide formation proceeded by direct delivery of oxidizing equivalents from Ero1p to folding substrates via PDI. This kinetic shuttling of oxidizing equivalents could allow the ER to support rapid disulfide formation while maintaining the ability to reduce and rearrange incorrect disulfide bonds.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tu, B P -- Ho-Schleyer, S C -- Travers, K J -- Weissman, J S -- New York, N.Y. -- Science. 2000 Nov 24;290(5496):1571-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Howard Hughes Medical Institute, Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94143, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11090354" target="_blank"〉PubMed〈/a〉
Keywords:
Binding Sites
;
Carboxypeptidases/chemistry/metabolism
;
Cathepsin A
;
Chemistry, Physical
;
Disulfides/chemistry
;
Endoplasmic Reticulum/*metabolism
;
Flavin-Adenine Dinucleotide/*metabolism
;
Glutathione/metabolism
;
Glycoproteins/*metabolism
;
Microsomes/metabolism
;
Mutation
;
Oxidation-Reduction
;
Oxidoreductases Acting on Sulfur Group Donors
;
Physicochemical Phenomena
;
Protein Disulfide-Isomerases/genetics/*metabolism
;
*Protein Folding
;
Ribonuclease, Pancreatic/chemistry/metabolism
;
Saccharomyces cerevisiae/metabolism
;
*Saccharomyces cerevisiae Proteins
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
