Crystallographic Analysis of thePseudomonas aeruginosaStrain K122-4 Monomeric Pilin Reveals a Conserved Receptor-Binding Architecture,

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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 (ΔK122-4) at 1.54 and 1.8 Å resolution, respectively. The ΔK122-4 structure is compared to other crystallographically determined type IV pilin structures and an NMR structure of ΔK122-4 pilin. A comparison with the structure of the highly divergent P. aeruginosa strain K (ΔPAK) 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.