7sk4: Difference between revisions

From Proteopedia
Jump to navigation Jump to search
New page: '''Unreleased structure''' The entry 7sk4 is ON HOLD Authors: Description: Category: Unreleased Structures
 
No edit summary
 
(6 intermediate revisions by the same user not shown)
Line 1: Line 1:
'''Unreleased structure'''


The entry 7sk4 is ON HOLD
==Cryo-EM structure of ACKR3 in complex with chemokine N-terminal mutant CXCL12_LRHQ, an intracellular Fab, and an extracellular Fab==
<StructureSection load='7sk4' size='340' side='right'caption='[[7sk4]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7sk4]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7SK4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SK4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=7sk4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sk4 OCA], [https://pdbe.org/7sk4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sk4 RCSB], [https://www.ebi.ac.uk/pdbsum/7sk4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sk4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACKR3_HUMAN ACKR3_HUMAN] Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Acts as coreceptor with CXCR4 for a restricted number of HIV isolates.<ref>PMID:16107333</ref> <ref>PMID:16940167</ref> <ref>PMID:17804806</ref> <ref>PMID:18653785</ref> <ref>PMID:19255243</ref> <ref>PMID:19380869</ref> <ref>PMID:19641136</ref> <ref>PMID:20018651</ref> <ref>PMID:20161793</ref> <ref>PMID:20388803</ref> <ref>PMID:20887389</ref> <ref>PMID:22300987</ref>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Both CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are activated by the chemokine CXCL12 yet evoke distinct cellular responses. CXCR4 is a canonical G protein-coupled receptor (GPCR), whereas ACKR3 is intrinsically biased for arrestin. The molecular basis for this difference is not understood. Here, we describe cryo-EM structures of ACKR3 in complex with CXCL12, a more potent CXCL12 variant, and a small-molecule agonist. The bound chemokines adopt an unexpected pose relative to those established for CXCR4 and observed in other receptor-chemokine complexes. Along with functional studies, these structures provide insight into the ligand-binding promiscuity of ACKR3, why it fails to couple to G proteins, and its bias toward beta-arrestin. The results lay the groundwork for understanding the physiological interplay of ACKR3 with other GPCRs.


Authors:  
Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias.,Yen YC, Schafer CT, Gustavsson M, Eberle SA, Dominik PK, Deneka D, Zhang P, Schall TJ, Kossiakoff AA, Tesmer JJG, Handel TM Sci Adv. 2022 Jul 15;8(28):eabn8063. doi: 10.1126/sciadv.abn8063. Epub 2022 Jul , 13. PMID:35857509<ref>PMID:35857509</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 7sk4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Gustavsson M]]
[[Category: Handel TM]]
[[Category: Schafer CT]]
[[Category: Tesmer JJG]]
[[Category: Yen YC]]

Latest revision as of 09:46, 21 November 2024

Cryo-EM structure of ACKR3 in complex with chemokine N-terminal mutant CXCL12_LRHQ, an intracellular Fab, and an extracellular FabCryo-EM structure of ACKR3 in complex with chemokine N-terminal mutant CXCL12_LRHQ, an intracellular Fab, and an extracellular Fab

Structural highlights

7sk4 is a 6 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.3Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACKR3_HUMAN Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Acts as coreceptor with CXCR4 for a restricted number of HIV isolates.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]

Publication Abstract from PubMed

Both CXC chemokine receptor 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are activated by the chemokine CXCL12 yet evoke distinct cellular responses. CXCR4 is a canonical G protein-coupled receptor (GPCR), whereas ACKR3 is intrinsically biased for arrestin. The molecular basis for this difference is not understood. Here, we describe cryo-EM structures of ACKR3 in complex with CXCL12, a more potent CXCL12 variant, and a small-molecule agonist. The bound chemokines adopt an unexpected pose relative to those established for CXCR4 and observed in other receptor-chemokine complexes. Along with functional studies, these structures provide insight into the ligand-binding promiscuity of ACKR3, why it fails to couple to G proteins, and its bias toward beta-arrestin. The results lay the groundwork for understanding the physiological interplay of ACKR3 with other GPCRs.

Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias.,Yen YC, Schafer CT, Gustavsson M, Eberle SA, Dominik PK, Deneka D, Zhang P, Schall TJ, Kossiakoff AA, Tesmer JJG, Handel TM Sci Adv. 2022 Jul 15;8(28):eabn8063. doi: 10.1126/sciadv.abn8063. Epub 2022 Jul , 13. PMID:35857509[13]

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

References

  1. ↑ Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F. The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes. J Biol Chem. 2005 Oct 21;280(42):35760-6. Epub 2005 Aug 17. PMID:16107333 doi:M508234200
  2. ↑ Burns JM, Summers BC, Wang Y, Melikian A, Berahovich R, Miao Z, Penfold ME, Sunshine MJ, Littman DR, Kuo CJ, Wei K, McMaster BE, Wright K, Howard MC, Schall TJ. A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med. 2006 Sep 4;203(9):2201-13. doi: 10.1084/jem.20052144. Epub 2006 Aug, 28. PMID:16940167 doi:http://dx.doi.org/10.1084/jem.20052144
  3. ↑ Sierro F, Biben C, Martinez-Munoz L, Mellado M, Ransohoff RM, Li M, Woehl B, Leung H, Groom J, Batten M, Harvey RP, Martinez-A C, Mackay CR, Mackay F. Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12/SDF-1 receptor, CXCR7. Proc Natl Acad Sci U S A. 2007 Sep 11;104(37):14759-64. doi:, 10.1073/pnas.0702229104. Epub 2007 Sep 5. PMID:17804806 doi:http://dx.doi.org/10.1073/pnas.0702229104
  4. ↑ Hartmann TN, Grabovsky V, Pasvolsky R, Shulman Z, Buss EC, Spiegel A, Nagler A, Lapidot T, Thelen M, Alon R. A crosstalk between intracellular CXCR7 and CXCR4 involved in rapid CXCL12-triggered integrin activation but not in chemokine-triggered motility of human T lymphocytes and CD34+ cells. J Leukoc Biol. 2008 Oct;84(4):1130-40. doi: 10.1189/jlb.0208088. Epub 2008 Jul, 24. PMID:18653785 doi:http://dx.doi.org/10.1189/jlb.0208088
  5. ↑ Kalatskaya I, Berchiche YA, Gravel S, Limberg BJ, Rosenbaum JS, Heveker N. AMD3100 is a CXCR7 ligand with allosteric agonist properties. Mol Pharmacol. 2009 May;75(5):1240-7. doi: 10.1124/mol.108.053389. Epub 2009 Mar , 2. PMID:19255243 doi:10.1124/mol.108.053389
  6. ↑ Levoye A, Balabanian K, Baleux F, Bachelerie F, Lagane B. CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein signaling. Blood. 2009 Jun 11;113(24):6085-93. doi: 10.1182/blood-2008-12-196618. Epub 2009 , Apr 20. PMID:19380869 doi:http://dx.doi.org/10.1182/blood-2008-12-196618
  7. ↑ Zabel BA, Wang Y, Lewen S, Berahovich RD, Penfold ME, Zhang P, Powers J, Summers BC, Miao Z, Zhao B, Jalili A, Janowska-Wieczorek A, Jaen JC, Schall TJ. Elucidation of CXCR7-mediated signaling events and inhibition of CXCR4-mediated tumor cell transendothelial migration by CXCR7 ligands. J Immunol. 2009 Sep 1;183(5):3204-11. doi: 10.4049/jimmunol.0900269. Epub 2009, Jul 29. PMID:19641136 doi:http://dx.doi.org/10.4049/jimmunol.0900269
  8. ↑ Rajagopal S, Kim J, Ahn S, Craig S, Lam CM, Gerard NP, Gerard C, Lefkowitz RJ. Beta-arrestin- but not G protein-mediated signaling by the "decoy" receptor CXCR7. Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):628-32. doi:, 10.1073/pnas.0912852107. Epub 2009 Dec 17. PMID:20018651 doi:http://dx.doi.org/10.1073/pnas.0912852107
  9. ↑ Naumann U, Cameroni E, Pruenster M, Mahabaleshwar H, Raz E, Zerwes HG, Rot A, Thelen M. CXCR7 functions as a scavenger for CXCL12 and CXCL11. PLoS One. 2010 Feb 11;5(2):e9175. doi: 10.1371/journal.pone.0009175. PMID:20161793 doi:http://dx.doi.org/10.1371/journal.pone.0009175
  10. ↑ Hattermann K, Held-Feindt J, Lucius R, Muerkoster SS, Penfold ME, Schall TJ, Mentlein R. The chemokine receptor CXCR7 is highly expressed in human glioma cells and mediates antiapoptotic effects. Cancer Res. 2010 Apr 15;70(8):3299-308. doi: 10.1158/0008-5472.CAN-09-3642. Epub , 2010 Apr 13. PMID:20388803 doi:http://dx.doi.org/10.1158/0008-5472.CAN-09-3642
  11. ↑ Tarnowski M, Liu R, Wysoczynski M, Ratajczak J, Kucia M, Ratajczak MZ. CXCR7: a new SDF-1-binding receptor in contrast to normal CD34(+) progenitors is functional and is expressed at higher level in human malignant hematopoietic cells. Eur J Haematol. 2010 Dec;85(6):472-83. doi: 10.1111/j.1600-0609.2010.01531.x. PMID:20887389 doi:http://dx.doi.org/10.1111/j.1600-0609.2010.01531.x
  12. ↑ Ray P, Mihalko LA, Coggins NL, Moudgil P, Ehrlich A, Luker KE, Luker GD. Carboxy-terminus of CXCR7 regulates receptor localization and function. Int J Biochem Cell Biol. 2012 Apr;44(4):669-78. doi:, 10.1016/j.biocel.2012.01.007. Epub 2012 Jan 25. PMID:22300987 doi:http://dx.doi.org/10.1016/j.biocel.2012.01.007
  13. ↑ Yen YC, Schafer CT, Gustavsson M, Eberle SA, Dominik PK, Deneka D, Zhang P, Schall TJ, Kossiakoff AA, Tesmer JJG, Handel TM. Structures of atypical chemokine receptor 3 reveal the basis for its promiscuity and signaling bias. Sci Adv. 2022 Jul 15;8(28):eabn8063. doi: 10.1126/sciadv.abn8063. Epub 2022 Jul, 13. PMID:35857509 doi:http://dx.doi.org/10.1126/sciadv.abn8063

7sk4, resolution 3.30Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=7sk4&oldid=4232958"