title: The crystal structure of pertussis toxin.
abstract: BACKGROUND
  Pertussis toxin is an exotoxin of the A-B class produced by Bordetella pertussis. The holotoxin comprises 952 residues forming six subunits (five different sequences, S1-S5). It plays an important role in the development of protective immunity to whooping cough, and is an essential component of new acellular vaccines. It is also widely used as a biochemical tool to ADP-ribosylate GTP-binding proteins in the study of signal transduction.
  
  
  RESULTS
  The crystal structure of pertussis toxin has been determined at 2.9 A resolution. The catalytic A-subunit (S1) shares structural homology with other ADP-ribosylating bacterial toxins, although differences in the carboxy-terminal portion explain its unique activation mechanism. Despite its heterogeneous subunit composition, the structure of the cell-binding B-oligomer (S2, S3, two copies of S4, and S5) resembles the symmetrical B-pentamers of the cholera toxin and Shiga toxin families, but it interacts differently with the A-subunit. The structural similarity is all the more surprising given that there is almost no sequence homology between B-subunits of the different toxins. Two peripheral domains that are unique to the pertussis toxin B-oligomer show unexpected structural homology with a calcium-dependent eukaryotic lectin, and reveal possible receptor-binding sites.
  
  
  CONCLUSIONS
  The structure provides insight into the pathogenic mechanisms of pertussis toxin and the evolution of bacterial toxins. Knowledge of the tertiary structure of the active site forms a rational basis for elimination of catalytic activity in recombinant molecules for vaccine use.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, University of Alberta, Edmonton, Canada.
authors.forename: P E
authors.initials: PE
authors.lastname: Stein
authors.forename: A
authors.initials: A
authors.lastname: Boodhoo
authors.forename: G D
authors.initials: GD
authors.lastname: Armstrong
authors.forename: S A
authors.initials: SA
authors.lastname: Cockle
authors.forename: M H
authors.initials: MH
authors.lastname: Klein
authors.forename: R J
authors.initials: RJ
authors.lastname: Read
mesh_terms: D000595:Amino Acid Sequence; D001886:Bordetella pertussis; D003196:Computer Graphics; D018360:Crystallography, X-Ray / Q000379:methods; D046911:Macromolecular Substances; D008958:Models, Molecular; D008969:Molecular Sequence Data; D037342:Pertussis Toxin; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid; D017356:Synchrotrons; D010566:Virulence Factors, Bordetella / Q000737:chemistry* / Q000302:isolation & purification; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D046911:Macromolecular Substances; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin