title: Crystal structure of the pertussis toxin-ATP complex: a molecular sensor.
abstract: Pertussis 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.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Hazes
authors.forename: A
authors.initials: A
authors.lastname: Boodhoo
authors.forename: S A
authors.initials: SA
authors.lastname: Cockle
authors.forename: R J
authors.initials: RJ
authors.lastname: Read
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D001692:Biological Transport; D003461:Crystallography; D004721:Endoplasmic Reticulum / Q000378:metabolism; D008958:Models, Molecular; D037342:Pertussis Toxin; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D017356:Synchrotrons; D010566:Virulence Factors, Bordetella / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D010566:Virulence Factors, Bordetella; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin