2x6l | pdb_00002x6l

X-ray Structure of Macrophage Inflammatory Protein-1 beta

spinqualitylabelsall models 2x6l, resolution 2.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2x6l is a 5 chain structure with sequence from Homo sapiens. This structure supersedes the now removed PDB entry 3kkh. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.602Å Ligands: GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. Publication Abstract from PubMed Macrophage inflammatory protein-1 (MIP-1), MIP-1alpha (CCL3) and MIP-1beta (CCL4) are chemokines crucial for immune responses towards infection and inflammation. Both MIP-1alpha and MIP-1beta form high-molecular-weight aggregates. Our crystal structures reveal that MIP-1 aggregation is a polymerization process and human MIP-1alpha and MIP-1beta form rod-shaped, double-helical polymers. Biophysical analyses and mathematical modelling show that MIP-1 reversibly forms a polydisperse distribution of rod-shaped polymers in solution. Polymerization buries receptor-binding sites of MIP-1alpha, thus depolymerization mutations enhance MIP-1alpha to arrest monocytes onto activated human endothelium. However, same depolymerization mutations render MIP-1alpha ineffective in mouse peritoneal cell recruitment. Mathematical modelling reveals that, for a long-range chemotaxis of MIP-1, polymerization could protect MIP-1 from proteases that selectively degrade monomeric MIP-1. Insulin-degrading enzyme (IDE) is identified as such a protease and decreased expression of IDE leads to elevated MIP-1 levels in microglial cells. Our structural and proteomic studies offer a molecular basis for selective degradation of MIP-1. The regulated MIP-1 polymerization and selective inactivation of MIP-1 monomers by IDE could aid in controlling the MIP-1 chemotactic gradient for immune surveillance. Polymerization of MIP-1 chemokine (CCL3 and CCL4) and clearance of MIP-1 by insulin-degrading enzyme.,Ren M, Guo Q, Guo L, Lenz M, Qian F, Koenen RR, Xu H, Schilling AB, Weber C, Ye RD, Dinner AR, Tang WJ EMBO J. 2010 Oct 19. PMID:20959807 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA