title: Oxidation state-dependent protein-protein interactions in disulfide cascades.
abstract: Bacterial growth and pathogenicity depend on the correct formation of disulfide bonds, a process controlled by the Dsb system in the periplasm of Gram-negative bacteria. Proteins with a thioredoxin fold play a central role in this process. A general feature of thiol-disulfide exchange reactions is the need to avoid a long lived product complex between protein partners. We use a multidisciplinary approach, involving NMR, x-ray crystallography, surface plasmon resonance, mutagenesis, and in vivo experiments, to investigate the interaction between the two soluble domains of the transmembrane reductant conductor DsbD. Our results show oxidation state-dependent affinities between these two domains. These observations have implications for the interactions of the ubiquitous thioredoxin-like proteins with their substrates, provide insight into the key role played by a unique redox partner with an immunoglobulin fold, and are of general importance for oxidative protein-folding pathways in all organisms.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
authors.forename: Despoina A I
authors.initials: DA
authors.lastname: Mavridou
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Saridakis
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Kritsiligkou
authors.forename: Alan D
authors.initials: AD
authors.lastname: Goddard
authors.forename: Julie M
authors.initials: JM
authors.lastname: Stevens
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Ferguson
authors.forename: Christina
authors.initials: C
authors.lastname: Redfield
mesh_terms: D018360:Crystallography, X-Ray; D004220:Disulfides / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000201:enzymology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D016296:Mutagenesis; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance
chemical_list: D004220:Disulfides; D029968:Escherichia coli Proteins; D010088:Oxidoreductases; C094848:DsbD electron transport protein, E coli