A Poly-Proline II Helix in YadA from Yersinia enterocolitica serotype O:9 Facilitates Heparin Binding through Electrostatic Interactions.

Poly-proline II helices are secondary structure motifs frequently found in ligand binding sites. They exhibit increased flexibility and solvent exposure compared to the strongly hydrogen-bonded α-helices or β-strands and can therefore easily be misinterpreted as completely unstructured regions with an extremely high rotational freedom. Here, we show that the adhesin YadA of Yersinia enterocolitica serotype O:9 contains a poly-proline II helix interaction motif in the N-terminal region. The motif is involved in the interaction of YadA O:9 with heparin, a host glycosaminoglycan. We show that the basic residues within the N-terminal motif of YadA are required for electrostatic interactions with the sulphate groups of heparin. Biophysical methods including CD spectroscopy, solution-state NMR, and SAXS all independently support the presence of a poly-proline helix allowing YadA O:9 binding to the rigid heparin. Lastly, we show that host cells deficient in sulphation of heparin and heparan sulphate are not targeted by YadA O:9 -mediated adhesion. We speculate that the YadA O:9 -heparin interaction plays an important and highly strain-specific role in the pathogenicity of Yersinia enterocolitica serotype O:9.