Crystal structure of viral macrophage inflammatory protein I encoded by Kaposi's sarcoma-associated herpesvirus at 1.7A.
Viral macrophage inflammatory protein I (vMIP-I) is a chemokine encoded by the Kaposi's sarcoma-associated herpesvirus (KSHV) that selectively activates the CC chemokine receptor 8 (CCR8), for which the endogenous ligand is CCL1. The crystal structure of vMIP-I was determined at 1.7A for comparison with other chemokines, especially those that bind CCR8, such as vMIP-II from KSHV, a CCR8 antagonist and the closest homolog (40% identical). vMIP-I has a typical chemokine fold consisting of an extended N-terminal loop, followed by a three-stranded antiparallel beta-sheet and a C-terminal alpha-helix. The four molecules in the asymmetric unit comprise two MIP-1beta-like dimers. Electrostatic surface representations of CCR8-binding chemokines reveal only minor areas of correlating surface potential, which must be reconciled with promiscuity in receptor and glycosaminoglycan (GAG) binding. In addition, the biological relevance of chemokine oligomerization is examined by comparing the oligomeric states of all chemokine structures deposited to date in the RCSB PDB.
Luz
John G
JG
Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Yu
Minmin
M
Su
Ying
Y
Wu
Zining
Z
Zhou
Zhou
Z
Sun
Ren
R
Wilson
Ian A
IA
D000595:Amino Acid Sequence; D054407:Chemokine CCL4; D018360:Crystallography, X-Ray; D006025:Glycosaminoglycans / Q000378:metabolism; D019288:Herpesvirus 8, Human / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D019402:Macrophage Inflammatory Proteins / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000821:virology*; D055672:Static Electricity
C103330:CCR8 protein, human; D054407:Chemokine CCL4; D006025:Glycosaminoglycans; D019402:Macrophage Inflammatory Proteins; D054401:Receptors, CCR8; D019707:Receptors, Chemokine