Crystal structure of Pseudomonas aeruginosa PAK pilin suggests a main-chain-dominated mode of receptor binding

Fibers of pilin monomers (pili) form the dominant adhesin of Pseudomonas ae ruginosa, and they play an important role in infections by this opportunist ic bacterial pathogen. Blocking adhesion is therefore a target for vaccine development. The receptor-binding site is located in a C-terminal disulphid e-bonded loop of each pilin monomer, but functional binding sites are displ ayed only at the tip of the pilus. A factor complicating vaccination is tha t different bacterial strains produce distinct, and sometimes highly diverg ent, pilin variants. It is surprising that all strains still appear to bind a common receptor, asialo-GM1. Here, we present the 1.63 Angstrom 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 therefo re be maintained, whilst allowing side-chain variation, if the main-chain c onformation 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 st ructure-based design of a consensus sequence vaccine. (C) 2000 Academic Pre ss.