title: Crystal structure of Pseudomonas aeruginosa PAK pilin suggests a main-chain-dominated mode of receptor binding.
abstract: Fibers of pilin monomers (pili) form the dominant adhesin of Pseudomonas aeruginosa, and they play an important role in infections by this opportunistic bacterial pathogen. Blocking adhesion is therefore a target for vaccine development. The receptor-binding site is located in a C-terminal disulphide-bonded loop of each pilin monomer, but functional binding sites are displayed only at the tip of the pilus. A factor complicating vaccination is that different bacterial strains produce distinct, and sometimes highly divergent, pilin variants. It is surprising that all strains still appear to bind a common receptor, asialo-GM1. Here, we present the 1.63 A crystal structure of pilin from P. aeruginosa strain PAK. The structure shows that the proposed receptor-binding site is formed by two beta-turns that create a surface dominated by main-chain atoms. Receptor specificity could therefore be maintained, whilst allowing side-chain variation, if the main-chain conformation is conserved. The location of the binding site relative to the proposed packing of the pilus fiber raises new issues and suggests that the current fiber model may have to be reconsidered. Finally, the structure of the C-terminal disulphide-bonded loop will provide the template for the structure-based design of a consensus sequence vaccine.
authors.affiliation: Department of Medical Microbiology and Immunology, Canadian Bacterial Diseases Network, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada. bart.hazes@ualberta.ca
authors.forename: B
authors.initials: B
authors.lastname: Hazes
authors.forename: P A
authors.initials: PA
authors.lastname: Sastry
authors.forename: K
authors.initials: K
authors.lastname: Hayakawa
authors.forename: R J
authors.initials: RJ
authors.lastname: Read
authors.forename: R T
authors.initials: RT
authors.lastname: Irvin
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism; D001428:Bacterial Vaccines / Q000737:chemistry; D001665:Binding Sites; D003460:Crystallization; D018360:Crystallography, X-Ray; D004220:Disulfides / Q000378:metabolism; D036781:Fimbriae Proteins; D005677:G(M1) Ganglioside / Q000378:metabolism; D006031:Glycosylation; D008565:Membrane Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000145:classification*; D016415:Sequence Alignment; D013379:Substrate Specificity; D014614:Vaccines, Synthetic / Q000737:chemistry
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D004220:Disulfides; D008565:Membrane Proteins; D010446:Peptide Fragments; D014614:Vaccines, Synthetic; D036781:Fimbriae Proteins; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside