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SOLUTION STRUCTURE OF THE CHEMOKINE HMIP-1BETA(SLASH)ACT-2 BY MULTI-DIMENSIONAL NMR: A NOVEL CHEMOKINE DIMER
Structural highlights
FunctionCCL4_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 PubMedThe three-dimensional structure of a member of the beta subfamily of chemokines, human macrophage inflammatory protein-1 beta (hMIP-1 beta), has been determined with the use of solution multidimensional heteronuclear magnetic resonance spectroscopy. Human MIP-1 beta is a symmetric homodimer with a relative molecular mass of approximately 16 kilodaltons. The structure of the hMIP-1 beta monomer is similar to that of the related alpha chemokine interleukin-8 (IL-8). However, the quaternary structures of the two proteins are entirely distinct, and the dimer interface is formed by a completely different set of residues. Whereas the IL-8 dimer is globular, the hMIP-1 beta dimer is elongated and cylindrical. This provides a rational explanation for the absence of cross-binding and reactivity between the alpha and beta chemokine subfamilies. Calculation of the solvation free energies of dimerization suggests that the formation and stabilization of the two different types of dimers arise from the burial of hydrophobic residues. High-resolution solution structure of the beta chemokine hMIP-1 beta by multidimensional NMR.,Lodi PJ, Garrett DS, Kuszewski J, Tsang ML, Weatherbee JA, Leonard WJ, Gronenborn AM, Clore GM Science. 1994 Mar 25;263(5154):1762-7. PMID:8134838[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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