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7f1t

From Proteopedia

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Current revision

Crystal structure of the human chemokine receptor CCR5 in complex with MIP-1a

Structural highlights

7f1t is a 1 chain structure with sequence from Clostridium pasteurianum and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CCR5_HUMAN Genetic variation in CCR5 is associated with susceptibility to diabetes mellitus insulin-dependent type 22 (IDDM22) [MIM: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.^[1]

Function

CCL3_HUMAN Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV).^[2] 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.^[3] ^[4] ^[5] ^[6] ^[7] ^[8] RUBR_CLOPA Rubredoxin is a small nonheme, iron protein lacking acid-labile sulfide. Its single Fe, chelated to 4 Cys, functions as an electron acceptor and may also stabilize the conformation of the molecule.

Publication Abstract from PubMed

The chemokine receptor CCR5 plays a vital role in immune surveillance and inflammation. However, molecular details that govern its endogenous chemokine recognition and receptor activation remain elusive. Here we report three cryo-electron microscopy structures of Gi1 protein-coupled CCR5 in a ligand-free state and in complex with the chemokine MIP-1alpha or RANTES, as well as the crystal structure of MIP-1alpha-bound CCR5. These structures reveal distinct binding modes of the two chemokines and a specific accommodate pattern of the chemokine for the distal N terminus of CCR5. Together with functional data, the structures demonstrate that chemokine-induced rearrangement of toggle switch and plasticity of the receptor extracellular region are critical for receptor activation, while a conserved tryptophan residue in helix II acts as a trigger of receptor constitutive activation.

Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5.,Zhang H, Chen K, Tan Q, Shao Q, Han S, Zhang C, Yi C, Chu X, Zhu Y, Xu Y, Zhao Q, Wu B Nat Commun. 2021 Jul 6;12(1):4151. doi: 10.1038/s41467-021-24438-5. PMID:34230484^[9]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Smyth DJ, Plagnol V, Walker NM, Cooper JD, Downes K, Yang JH, Howson JM, Stevens H, McManus R, Wijmenga C, Heap GA, Dubois PC, Clayton DG, Hunt KA, van Heel DA, Todd JA. Shared and distinct genetic variants in type 1 diabetes and celiac disease. N Engl J Med. 2008 Dec 25;359(26):2767-77. doi: 10.1056/NEJMoa0807917. Epub 2008 , Dec 10. PMID:19073967 doi:10.1056/NEJMoa0807917
↑ 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
↑ Samson M, Labbe O, Mollereau C, Vassart G, Parmentier M. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry. 1996 Mar 19;35(11):3362-7. PMID:8639485 doi:10.1021/bi952950g
↑ Raport CJ, Gosling J, Schweickart VL, Gray PW, Charo IF. Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1beta, and MIP-1alpha. J Biol Chem. 1996 Jul 19;271(29):17161-6. PMID:8663314
↑ Combadiere C, Ahuja SK, Tiffany HL, Murphy PM. Cloning and functional expression of CC CKR5, a human monocyte CC chemokine receptor selective for MIP-1(alpha), MIP-1(beta), and RANTES. J Leukoc Biol. 1996 Jul;60(1):147-52. PMID:8699119
↑ Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR. Identification of a major co-receptor for primary isolates of HIV-1. Nature. 1996 Jun 20;381(6584):661-6. PMID:8649511 doi:10.1038/381661a0
↑ Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, Paxton WA. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature. 1996 Jun 20;381(6584):667-73. PMID:8649512 doi:10.1038/381667a0
↑ Blanpain C, Wittamer V, Vanderwinden JM, Boom A, Renneboog B, Lee B, Le Poul E, El Asmar L, Govaerts C, Vassart G, Doms RW, Parmentier M. Palmitoylation of CCR5 is critical for receptor trafficking and efficient activation of intracellular signaling pathways. J Biol Chem. 2001 Jun 29;276(26):23795-804. Epub 2001 Apr 25. PMID:11323418 doi:10.1074/jbc.M100583200
↑ Zhang H, Chen K, Tan Q, Shao Q, Han S, Zhang C, Yi C, Chu X, Zhu Y, Xu Y, Zhao Q, Wu B. Structural basis for chemokine recognition and receptor activation of chemokine receptor CCR5. Nat Commun. 2021 Jul 6;12(1):4151. doi: 10.1038/s41467-021-24438-5. PMID:34230484 doi:http://dx.doi.org/10.1038/s41467-021-24438-5

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7f1t"

@@ Line 3: / Line 3: @@
 <StructureSection load='7f1t' size='340' side='right'caption='[[7f1t]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7f1t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/"bacillus_pasteurianus"_(winogradsky_1895)_lehmann_and_neumann_1907 "bacillus pasteurianus" (winogradsky 1895) lehmann and neumann 1907]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F1T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F1T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[7f1t]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Clostridium_pasteurianum Clostridium pasteurianum] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F1T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F1T FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.6&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CCR5, CMKBR5 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1501 "Bacillus pasteurianus" (Winogradsky 1895) Lehmann and Neumann 1907])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=7f1t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f1t OCA], [https://pdbe.org/7f1t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f1t RCSB], [https://www.ebi.ac.uk/pdbsum/7f1t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f1t 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/CCL3_HUMAN CCL3_HUMAN]] Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV).<ref>PMID:8525373</ref>
+[https://www.uniprot.org/uniprot/CCL3_HUMAN CCL3_HUMAN] Monokine with inflammatory and chemokinetic properties. Binds to CCR1, CCR4 and CCR5. One of the major HIV-suppressive factors produced by CD8+ T-cells. Recombinant MIP-1-alpha induces a dose-dependent inhibition of different strains of HIV-1, HIV-2, and simian immunodeficiency virus (SIV).<ref>PMID:8525373</ref> [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> [https://www.uniprot.org/uniprot/RUBR_CLOPA RUBR_CLOPA] Rubredoxin is a small nonheme, iron protein lacking acid-labile sulfide. Its single Fe, chelated to 4 Cys, functions as an electron acceptor and may also stabilize the conformation of the molecule.
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Clostridium pasteurianum]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Chen, K]]
+[[Category: Chen K]]
-[[Category: Han, S]]
+[[Category: Han S]]
-[[Category: Tan, Q]]
+[[Category: Tan Q]]
-[[Category: Wu, B]]
+[[Category: Wu B]]
-[[Category: Zhang, H]]
+[[Category: Zhang H]]
-[[Category: Zhao, Q]]
+[[Category: Zhao Q]]
-[[Category: Zhu, Y]]
+[[Category: Zhu Y]]
-[[Category: Chemokine receptor ccr5]]
-[[Category: G protein-coupled receptor]]
-[[Category: Mip-1a]]
-[[Category: Signaling protein]]

7f1t

From Proteopedia

Current revision

Crystal structure of the human chemokine receptor CCR5 in complex with MIP-1a

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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