Crystallographic analysis of the Pseudomonas aeruginosa strain K122-4 monomeric pilin reveals a conserved receptor-binding architecture.
Adherence of pathogens to host cells is critical for the initiation of infection and is thus an attractive target for anti-infective therapeutics and vaccines. In the opportunistic human pathogen Pseudomonas aeruginosa, host-cell adherence is achieved predominantly by type IV pili. Analysis of several clinical strains of P. aeruginosa reveals poor sequence conservation between pilin genes, including the residues in the receptor-binding site. Interestingly, the receptor-binding sites appear to retain a conserved surface epitope because all Pseudomonas type IV pili recognize the same receptor on the host cell and cross-reactive antibodies specific for the receptor-binding site exist. Here, we present the crystallographic analysis of two crystal forms of truncated pilin from P. aeruginosa strain K122-4 (DeltaK122-4) at 1.54 and 1.8 A resolution, respectively. The DeltaK122-4 structure is compared to other crystallographically determined type IV pilin structures and an NMR structure of DeltaK122-4 pilin. A comparison with the structure of the highly divergent P. aeruginosa strain K (DeltaPAK) pilin indicates that the receptor-binding loop in both pilins forms a shallow depression with a surface that is formed by main-chain atoms. Conservation of this putative binding site is independent of the sequence as long as the main-chain conformation is conserved and could therefore explain the shared receptor specificity and antibody cross reactivity of highly divergent Pseudomonas type IV pilins.
Audette
Gerald F
GF
Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7.
Irvin
Randall T
RT
Hazes
Bart
B
D001665:Binding Sites; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D036781:Fimbriae Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D009344:Neisseria gonorrhoeae / Q000737:chemistry; D018933:Pili, Sex / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000737:chemistry* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000378:metabolism*; D014734:Vibrio cholerae / Q000737:chemistry
D011971:Receptors, Immunologic; C037872:pili, bacterial receptor; D036781:Fimbriae Proteins