Crystallographic studies of chemokine receptors and their ligands

Division Of Clinical Sciences - Nci

Investigators

Linked publications & trials

Abstract

One of the most significant accomplishments was to show a strong inhibitory properties of human defensin 5 (HD5) against the papillomaviruses. These properties make HD5 a potential candidate for the topical agent in preventing the papillomavirus infection. This year we also published the first structural data on three human alpha-defensis, HNP4, HD5, and HD6. This accomplishment makes all human alpha-defensins structurally characterized. In the other study, we published the preliminary draft of the epitope in the human beta-defensin molecules, that is responsible for binding and/or activating the chemokine receptor, CCR6. In continuation of this effort, whcih is near-complete, we identified more details on the structural determinants of beta-defensins, whcih are necessary for productive interaction with CCR6. We also showed that one of these proteins, hBD4, does not activate CCR6 and explained, in detail, the reason for this defficiency. In collaboration with Dr. Lu, we studies two other aspects of human alpha-defensins'chemistry: high ratio of Arg (as compared to Lys) in their sequences, the phenomenon not observed for beta-defensins, and effect of the pro-region, in a pro-peptide form, for the folding efficiency of human alpha-defensins. In both cases, we provided a rationalization, based largery on structural studies.