501. Quality control of disulfide bond formation in pilus subunits by the chaperone FimC
- Author
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Oliv Eidam, Maria D Crespo, Martin A. Schärer, Rudi Glockshuber, Markus G. Grütter, Guido Capitani, Chasper Puorger, University of Zurich, and Glockshuber, Rudi
- Subjects
Models, Molecular ,Protein Folding ,Protein Conformation ,Protein subunit ,Pilus ,1307 Cell Biology ,03 medical and health sciences ,Protein structure ,10019 Department of Biochemistry ,1312 Molecular Biology ,Uropathogenic Escherichia coli ,Disulfides ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,biology ,Escherichia coli Proteins ,Oxidative folding ,030302 biochemistry & molecular biology ,Gene Expression Regulation, Bacterial ,Cell Biology ,Periplasmic space ,biochemical phenomena, metabolism, and nutrition ,Kinetics ,Protein Subunits ,DsbA ,Biochemistry ,Fimbriae, Bacterial ,Chaperone (protein) ,biology.protein ,Biophysics ,570 Life sciences ,bacteria ,Protein folding ,Fimbriae Proteins ,Oxidation-Reduction ,Protein Binding - Abstract
Type 1 pili from uropathogenic Escherichia coli are filamentous, noncovalent protein complexes mediating bacterial adhesion to the host tissue. All structural pilus subunits are homologous proteins sharing an invariant disulfide bridge. Here we show that disulfide bond formation in the unfolded subunits, catalyzed by the periplasmic oxidoreductase DsbA, is required for subunit recognition by the assembly chaperone FimC and for FimC-catalyzed subunit folding. FimC thus guarantees quantitative disulfide bond formation in each of the up to 3,000 subunits of the pilus. The X-ray structure of the complex between FimC and the main pilus subunit FimA and the kinetics of FimC-catalyzed FimA folding indicate that FimC accelerates folding of pilus subunits by lowering their topological complexity. The kinetic data, together with the measured in vivo concentrations of DsbA and FimC, predict an in vivo half-life of 2 s for oxidative folding of FimA in the periplasm.
- Published
- 2012
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