Structural highlights
Function
[CCL4_HUMAN] Monokine with inflammatory and chemokinetic properties. Binds to CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-beta induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV). The processed form MIP-1-beta(3-69) retains the abilities to induce down-modulation of surface expression of the chemokine receptor CCR5 and to inhibit the CCR5-mediated entry of HIV-1 in T-cells. MIP-1-beta(3-69) is also a ligand for CCR1 and CCR2 isoform B.[1] [2] [3]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
Solution structure of the complex between poxvirus-encoded CC chemokine inhibitor vCCI and human MIP-1beta.,Zhang L, Derider M, McCornack MA, Jao SC, Isern N, Ness T, Moyer R, LiWang PJ Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):13985-90. Epub 2006 Sep 8. PMID:16963564[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, Lusso P. Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science. 1995 Dec 15;270(5243):1811-5. PMID:8525373
- ↑ Garlisi CG, Xiao H, Tian F, Hedrick JA, Billah MM, Egan RW, Umland SP. The assignment of chemokine-chemokine receptor pairs: TARC and MIP-1 beta are not ligands for human CC-chemokine receptor 8. Eur J Immunol. 1999 Oct;29(10):3210-5. PMID:10540332 doi:http://dx.doi.org/10.1002/(SICI)1521-4141(199910)29:10<3210::AID-IMMU3210>3.0.CO;2-W
- ↑ Guan E, Wang J, Roderiquez G, Norcross MA. Natural truncation of the chemokine MIP-1 beta /CCL4 affects receptor specificity but not anti-HIV-1 activity. J Biol Chem. 2002 Aug 30;277(35):32348-52. Epub 2002 Jun 17. PMID:12070155 doi:http://dx.doi.org/10.1074/jbc.M203077200
- ↑ Zhang L, Derider M, McCornack MA, Jao SC, Isern N, Ness T, Moyer R, LiWang PJ. Solution structure of the complex between poxvirus-encoded CC chemokine inhibitor vCCI and human MIP-1beta. Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):13985-90. Epub 2006 Sep 8. PMID:16963564
