title: Turning a disulfide isomerase into an oxidase: DsbC mutants that imitate DsbA.
abstract: There are two distinct pathways for disulfide formation in prokaryotes. The DsbA-DsbB pathway introduces disulfide bonds de novo, while the DsbC-DsbD pathway functions to isomerize disulfides. One of the key questions in disulfide biology is how the isomerase pathway is kept separate from the oxidase pathway in vivo. Cross-talk between these two systems would be mutually destructive. To force communication between these two systems we have selected dsbC mutants that complement a dsbA null mutation. In these mutants, DsbC is present as a monomer as compared with dimeric wild-type DsbC. Based on these findings we rationally designed DsbC mutants in the dimerization domain. All of these mutants are able to rescue the dsbA null phenotype. Rescue depends on the presence of DsbB, the native re-oxidant of DsbA, both in vivo and in vitro. Our results suggest that dimerization acts to protect DsbC's active sites from DsbB-mediated oxidation. These results explain how oxidative and reductive pathways can co-exist in the periplasm of Escherichia coli.
authors: Department of Biology and Medical Scientist Training Program, University of Michigan, Ann Arbor, MI 48109-1048, USA.
authors: M W
authors: MW
authors: Bader
authors: A
authors: A
authors: Hiniker
authors: J
authors: J
authors: Regeimbal
authors: D
authors: D
authors: Goldstone
authors: P W
authors: PW
authors: Haebel
authors: J
authors: J
authors: Riemer
authors: P
authors: P
authors: Metcalf
authors: J C
authors: JC
authors: Bardwell
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D016296:Mutagenesis; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017433:Protein Structure, Secondary
chemical_list: D001426:Bacterial Proteins; C079503:DsbB protein, Bacteria; D008565:Membrane Proteins; D010088:Oxidoreductases; D019704:Protein Disulfide-Isomerases