Structural characteristics of potential novel virulence factors, the host cytokine binding proteins of Aggregatibacter actinomycetemcomitans

Various gram-negative pathogens possess secreted or outer membrane proteins (OMPs) which interact with host cytokines. Of periodontal pathogens only Aggregatibacter actinomycetemcomitans (Aa) has been shown to sequester and uptake cytokines. We have identified two (OMPs) of Aa, bacterial interleukin receptor I (BilRI) and OM secretin channel (OMS), which interact with several cytokines, the interaction with IL-8 being the strongest. The NMR studies confirmed that BilRI is intrinsically disordered, i.e. it does not have stabile fold without ligand. The structure of the extramembranous domains of OMS (emOMS) solved with X-ray crystallography showed that the C-terminal domain of emOMS displayed a type I KH domain fold. Crosslinking experiments indicate that one lysine of this domain is located in the IL-8 interaction site. Neisseria meningitides PilQ (NmPilQ) has role in the uptake of IL-8. Although the part of the NmPilQ which interacts with IL-8 is unidentified, the N1-domain of NmPilQ shows sequence homology and adopts the same fold as the C-terminal domain of emOMS. Thus the type I KH domain fold might be involved in the cytokine interaction in both these bacterial proteins. It would be interesting to learn if type I KH domains can be found from other periodontal pathogens than Aa.