Solution structure of the complex between poxvirus-encoded CC chemokine inhibitor vCCI and human MIP-1beta.
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.
Zhang
Li
L
Department of Biochemistry and Biophysics, Texas A&M University, College Station, TX 77843-2128, USA.
Derider
Michele
M
McCornack
Melissa A
MA
Jao
Shu-Chuan
SC
Isern
Nancy
N
Ness
Traci
T
Moyer
Richard
R
LiWang
Patricia J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D011212:Poxviridae / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D011817:Rabbits; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D037521:Virulence Factors
C414049:CCI protein, Cowpox virus; C066507:CCL4 protein, human; D054407:Chemokine CCL4; D019742:Chemokines, CC; D046912:Multiprotein Complexes; D014764:Viral Proteins; D037521:Virulence Factors