NMR solution structure of murine CCL20/MIP-3 alpha, a chemokine that specifically chemoattracts immature dendritic cells and lymphocytes through its highly specific interaction with the beta-chemokine receptor CCR6

CCL20/MIP-3 alpha is a beta -chemokine expressed in the thymus, skin, and i ntestinal epithelial cells that exclusively binds and activates the CCR6 re ceptor in both mice and humans. The strict receptor binding specificity of CCL20 is exceptional; other chemokines and their receptors bind promiscuous ly with multiple partners. Toward determining the structural basis for the selective receptor specificity of CCL20, we have determined its three-dimen sional structure by H-1 NMR spectroscopy. CCL20 exhibits the same monomeric structure previously described for other chemokines: a three-stranded beta -sheet and an overlying alpha -helix. The CCL20 receptor selectivity could arise from the rigid conformation of the N-terminal DCCL motif as well as the groove between the N-loop and the beta (2)-beta (3) hairpin, which is s ignificantly narrower in CCL20 than in other chemokines. Similar structural features are seen in human beta -defensin 2, a small nonchemokine polypept ide reported to selectively bind and activate CCR6, which stresses their im portance for the specific binding of both CCL20 and beta -defensin 2 to CCR 6. CCL20's structure will be useful to design tools aimed to modulate its i mportant biological functions.