1bcp | pdb_00001bcp
BINARY COMPLEX OF PERTUSSIS TOXIN AND ATP
Structural highlights
FunctionTOX1_BORPE S1 is an NAD-dependent ADP-ribosyltransferase, which plays a crucial role in the pathogenesis of B.pertussis causing disruption of normal host cellular regulation. It catalyzes the ADP-ribosylation of a cysteine in the alpha subunit of host heterotrimeric G proteins. In the absence of G proteins it also catalyzes the cleavage of NAD(+) into ADP-ribose and nicotinamide. It irreversibly uncouples the G-alpha GTP-binding proteins from their membrane receptors. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPertussis toxin is a major virulence factor of Bordetella pertussis, the causative agent of whooping cough. The protein is a hexamer containing a catalytic subunit (S1) that is tightly associated with a pentameric cell-binding component (B-oligomer). In vitro experiments have shown that ATP and a number of detergents and phospholipids assist in activating the holotoxin by destabilizing the interaction between S1 and the B-oligomer. Similar processes may play a role in the activation of pertussis toxin in vivo. In this paper we present the crystal structure of the pertussis toxin-ATP complex and discuss the structural basis for the ATP-induced activation. In addition, we propose a physiological role for the ATP effect in the process by which the toxin enters the cytoplasm of eukaryotic cells. The key features of this proposal are that ATP binding signals the arrival of the toxin in the endoplasmic reticulum and, at the same time, triggers dissociation of the holotoxin prior to membrane translocation. Crystal structure of the pertussis toxin-ATP complex: a molecular sensor.,Hazes B, Boodhoo A, Cockle SA, Read RJ J Mol Biol. 1996 May 17;258(4):661-71. PMID:8637000[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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