2mzx
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | The entry 2mzx | + | ==CCR5-ECL2 helical structure, residues Q186-T195== |
| + | <StructureSection load='2mzx' size='340' side='right'caption='[[2mzx]]' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[2mzx]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MZX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MZX FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2mzx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mzx OCA], [https://pdbe.org/2mzx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mzx RCSB], [https://www.ebi.ac.uk/pdbsum/2mzx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mzx ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/CCR5_HUMAN CCR5_HUMAN] Genetic variation in CCR5 is associated with susceptibility to diabetes mellitus insulin-dependent type 22 (IDDM22) [MIM:[https://omim.org/entry/612522 612522]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:19073967</ref> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/CCR5_HUMAN CCR5_HUMAN] Receptor for a number of inflammatory CC-chemokines including MIP-1-alpha, MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation. Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 R5 isolates.<ref>PMID:8639485</ref> <ref>PMID:8663314</ref> <ref>PMID:8699119</ref> <ref>PMID:8649511</ref> <ref>PMID:8649512</ref> <ref>PMID:11323418</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | C-C chemokine receptor 5 (CCR5) serves as a co-receptor for HIV-1. The CCR5 N-terminal segment, the second extracellular loop (ECL2) and the transmembrane helices have been implicated in binding the envelope glycoprotein gp120. Peptides corresponding to the sequence of the putative ECL2 as well as peptides containing extracellular loops 1 and 3 (ECL1 and ECL3) were found to inhibit HIV-1 infection. The aromatic residues in the C-terminal half of an ECL2 peptide were shown to interact with gp120. In the present study, we found that, in aqueous buffer, the segment Q188-Q194 in an elongated ECL2 peptide (R168-K197) forms an amphiphilic helix, which corresponds to the beginning of the fifth transmembrane helix in the crystal structure of CCR5. Two-dimensional saturation transfer difference NMR spectroscopy and dynamic filtering studies revealed involvement of Y187, F189, W190 and F193 of the helical segment in the interaction with gp120. The crystal structure of CCR5 shows that the aromatic side chains of F189, W190 and F193 point away from the binding pocket and interact with the membrane or with an adjacent CCR5 molecule, and therefore could not interact with gp120 in the intact CCR5 receptor. We conclude that these three aromatic residues of ECL2 peptides interact with gp120 through hydrophobic interactions that are not representative of the interactions of the intact CCR5 receptor. The HIV-1 inhibition by ECL2 peptides, as well as by ECL1 and ECL3 peptides and peptides corresponding to ECL2 of CXCR4, which serves as an alternative HIV-1 co-receptor, suggests that there is a hydrophobic surface in the envelope spike that could be a target for HIV-1 entry inhibitors. DATABASE: The structures and NMR data of ECL2S (Q186-T195) were deposited under Protein Data Bank ID 2mzx and BioMagResBank ID 25505. | ||
| - | + | An extended CCR5 ECL2 peptide forms a helix that binds HIV-1 gp120 through non-specific hydrophobic interactions.,Abayev M, Moseri A, Tchaicheeyan O, Kessler N, Arshava B, Naider F, Scherf T, Anglister J FEBS J. 2015 Feb 20. doi: 10.1111/febs.13243. PMID:25703038<ref>PMID:25703038</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: Abayev | + | <div class="pdbe-citations 2mzx" style="background-color:#fffaf0;"></div> |
| - | [[Category: Anglister | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Abayev M]] | ||
| + | [[Category: Anglister J]] | ||
Current revision
CCR5-ECL2 helical structure, residues Q186-T195
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