Solution structure of the complex between poxvirus-encoded CC chemokine inhibitor vCCI and human MIP-1b

Solution structure of the complex between poxvirus-encoded

CC chemokine inhibitor vCCI and human MIP-1b

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Abstract

Chemokines (chemotactic cytokines) comprise a large family of proteins that recruit and activate leukocytes, giving chemokines a major role in both immune response and inflammation-related diseases. The poxvirus-encoded viral CC chemokine inhibitor (vCCI) binds to many CC chemokines with high affinity, acting as a potent inhibitor of chemokine action. We have used heteronuclear multidimensional NMR to determine the first structure of an orthopoxvirus vCCI in complex with a human CC chemokine MIP-1b. vCCI binds to the chemokine with 1:1 stoichiometry, forming a complex of 311 amino acids. vCCI uses residues from its b-sheet II to interact with a surface of MIP-1b that includes residues adjacent to its N-terminus, as well as residues in the 20’s region, and the 40’s loop. This structure reveals the strategy used by vCCI to tightly bind numerous chemokines, while retaining selectivity for the CC chemokine subfamily.