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


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 structure of an orthopoxvirus vCCI in complex with a human CC chemokine, MIP-1beta (macrophage inflammatory protein 1beta). vCCI binds to the chemokine with 1:1 stoichiometry, forming a complex of 311 aa. vCCI uses residues from its beta-sheet II to interact with a surface of MIP-1beta 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.

SUBMITTER: Zhang L 

PROVIDER: S-EPMC1599900 | biostudies-literature | 2006 Sep

REPOSITORIES: biostudies-literature

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

Zhang Li L   Derider Michele M   McCornack Melissa A MA   Jao Shu-Chuan SC   Isern Nancy N   Ness Traci T   Moyer Richard R   LiWang Patricia J PJ  

Proceedings of the National Academy of Sciences of the United States of America 20060908 38


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 structure of an orthopoxvirus vCCI in complex with a human CC chemokine, MIP-1bet  ...[more]

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