Oxidation state-dependent protein-protein interactions in disulfide cascades.

Journal article

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: Mavridou, D; Saridakis, E; Kritsiligkou, P; Goddard, A; Stevens, J

• Publication status: Published
• Journal: Journal of biological chemistry
• Volume: 286
• Issue: 28
• Pages: 24943-24956
• Publication date: 2011-07-01
• DOI: 10.1074/jbc.m111.236141
• EISSN: 1083-351X
• ISSN: 0021-9258
• Language: English
• Keywords: Mutagenesis; Crystallography, X-Ray; Disulfides; Oxidation-Reduction; Magnetic Resonance Spectroscopy; Protein Folding; Oxidoreductases; Surface Plasmon Resonance; Escherichia coli; Protein Structure, Tertiary; Escherichia coli Proteins