Crystallographic Analysis of the Pseudomonas Aeruginosa Strain K122-4 Monomeric Pilin Reveals a Conserved Receptor-Binding Architecture

Biochemistry. 2004 Sep 14;43(36):11427-35. doi: 10.1021/bi048957s.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Binding Sites
  • Conserved Sequence
  • Crystallography, X-Ray
  • Fimbriae Proteins / chemistry*
  • Fimbriae Proteins / classification
  • Fimbriae Proteins / metabolism*
  • Fimbriae, Bacterial / chemistry*
  • Fimbriae, Bacterial / metabolism*
  • Models, Molecular
  • Neisseria gonorrhoeae / chemistry
  • Pili, Sex / chemistry
  • Pili, Sex / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Tertiary
  • Pseudomonas aeruginosa / chemistry*
  • Pseudomonas aeruginosa / metabolism
  • Receptors, Immunologic / chemistry*
  • Receptors, Immunologic / metabolism*
  • Vibrio cholerae / chemistry

Substances

  • Receptors, Immunologic
  • pili, bacterial receptor
  • Fimbriae Proteins

Associated data

  • PDB/1QVE
  • PDB/1RG0