Structural study of the interaction between poxvirus-encoded cc chemokine inhibitor vcci and human mip-1beta

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Title: Structural study of the interaction between poxvirus-encoded cc chemokine inhibitor vcci and human mip-1beta
Author: Zhang, Li
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 . Viral CC chemokine inhibitor (vCCI ) is a poxvirus encoded protein that has been shown to bind tightly and inhibit the action of many CC chemokines . This function suggests that vCCI could be explored as an antiinflammatory therapeutic , a possibility that has been supported in mouse studies . The structure of vCCI in unbound form was determined by others , but to date no structure has been reported of bound vCCI . We report the NMR structure of vCCI in complex with the human CC chemokine MIP -1[beta] . The non -aggregating MIP -1[beta] variant MIP -1[beta] 45AASA48 was used in this complex to allow sufficiently high concentration at pH 7 to carry out the solution structure determination . A combination of NOE distance restraints , torsion angle restraints , and residual dipolar coupling were used to determine the structure of the complex , which also required protein deuteration due to its relatively large size (34kDa ) . The structure shows that MIP -1[beta] binds to vCCI with 1 :1 stoichiometry , forming a complex of 311 amino acids . vCCI uses residues from its [beta] - sheet II to interact with a surface of MIP -1[beta] that includes residues adjacent to its Nterminus , as well as residues in the 20's region , and the 40's loop . The structure of the MIP -1[beta] -vCCI complex reveals for the first time the regions of each protein involved in the interaction , and allows a greater understanding of the strategy used by vCCI to tightly bind numerous chemokines , while retaining selectivity for the CC chemokine subfamily .
URI: http : / /hdl .handle .net /1969 .1 /85901
Date: 2008-10-10

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Structural study of the interaction between poxvirus-encoded cc chemokine inhibitor vcci and human mip-1beta. Available electronically from http : / /hdl .handle .net /1969 .1 /85901 .

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