title: Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin.
abstract: Cholera toxin is assembled from two subunits in the periplasm of Vibrio cholerae and disassembled in the analogous compartment of target cells, the lumen of the endoplasmic reticulum (ER), before a fragment of it, the A1 chain, is transported into the cytosol. We show that protein disulfide isomerase (PDI) in the ER lumen functions to disassemble and unfold the toxin once its A chain has been cleaved. PDI acts as a redox-driven chaperone; in the reduced state, it binds to the A chain and in the oxidized state it releases it. Our results explain the pathway of cholera toxin, suggest a role for PDI in retrograde protein transport into the cytosol, and indicate that PDI can act as a novel type of chaperone, whose binding and release of substrates is regulated by a redox, rather than an ATPase, cycle.
authors: Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
authors: B
authors: B
authors: Tsai
authors: C
authors: C
authors: Rodighiero
authors: W I
authors: WI
authors: Lencer
authors: T A
authors: TA
authors: Rapoport
mesh_terms: D000818:Animals; D002772:Cholera Toxin / Q000737:chemistry / Q000378:metabolism*; D003001:Cloning, Molecular; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000378:metabolism; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010084:Oxidation-Reduction; D010179:Pancreas / Q000378:metabolism; D011489:Protein Denaturation; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D017510:Protein Folding; D021122:Protein Subunits; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D014734:Vibrio cholerae / Q000378:metabolism
chemical_list: D018832:Molecular Chaperones; D021122:Protein Subunits; D011994:Recombinant Proteins; D002772:Cholera Toxin; D019704:Protein Disulfide-Isomerases