Structural highlights
FunctionPublication Abstract from PubMedHuman beta-defensins (hBDs) are believed to function as alarm molecules that stimulate the adaptive immune system when a threat is present. In addition to its antimicrobial activity, defensins present other activities such as chemoattraction of a range of different cell types to the sites of inflammation. We have solved the structure of the hBD6 by NMR spectroscopy that contains a conserved beta-defensin domain followed by an extended C-terminus. We use NMR to monitor the interaction of hBD6 with microvesicles shed by breast cancer cell lines and with peptides derived from the extracellular domain of CC chemokine receptor 2 (Nt-CCR2) possessing or not possessing sulfation on Tyr26 and Tyr28. The NMR-derived model of the hBD6/CCR2 complex reveals a contiguous binding surface on hBD6, which comprises amino acid residues of the alpha-helix and beta2-beta3 loop. The microvesicle binding surface partially overlaps with the chemokine receptor interface. NMR spin relaxation suggests that free hBD6 and the hBD6/CCR2 complex exhibit microsecond-to-millisecond conformational dynamics encompassing the CCR2 binding site, which might facilitate selection of the molecular configuration optimal for binding. These data offer new insights into the structure-function relation of the hBD6-CCR2 interaction, which is a promising target for the design of novel anticancer agents. Structural Basis for the Interaction of Human beta-Defensin 6 and Its Putative Chemokine Receptor CCR2 and Breast Cancer Microvesicles.,De Paula VS, Gomes NS, Lima LG, Miyamoto CA, Monteiro RQ, Almeida FC, Valente AP J Mol Biol. 2013 Aug 11. pii: S0022-2836(13)00504-4. doi:, 10.1016/j.jmb.2013.08.001. PMID:23938203[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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