7tuy

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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7tuy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TUY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TUY FirstGlance]. <br>
<table><tr><td colspan='2'>[[7tuy]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TUY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TUY FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KKF:8-[(2E)-3-(4-chlorophenyl)prop-2-enoyl]-3-[(3,4-dichlorophenyl)methyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one'>KKF</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.98&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=KKF:8-[(~{E})-3-(4-chlorophenyl)prop-2-enoyl]-3-[(3,4-dichlorophenyl)methyl]-1-oxa-3,8-diazaspiro[4.5]decan-2-one'>KKF</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=7tuy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tuy OCA], [https://pdbe.org/7tuy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tuy RCSB], [https://www.ebi.ac.uk/pdbsum/7tuy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tuy ProSAT]</span></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=7tuy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tuy OCA], [https://pdbe.org/7tuy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tuy RCSB], [https://www.ebi.ac.uk/pdbsum/7tuy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tuy ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/GP183_HUMAN GP183_HUMAN]] G-protein coupled receptor expressed in lymphocytes that acts as a chemotactic receptor for B-cells, T-cells, splenic dendritic cells, monocytes/macrophages and astrocytes (By similarity). Receptor for oxysterol 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC) and other related oxysterols (PubMed:21796212, PubMed:22875855, PubMed:22930711). Mediates cell positioning and movement of a number of cells by binding the 7-alpha,25-OHC ligand that forms a chemotactic gradient (By similarity). Binding of 7-alpha,25-OHC mediates the correct localization of B-cells during humoral immune responses (By similarity). Guides B-cell movement along the B-cell zone-T-cell zone boundary and later to interfollicular and outer follicular regions (By similarity). Its specific expression during B-cell maturation helps position B-cells appropriately for mounting T-dependent antibody responses (By similarity). Collaborates with CXCR5 to mediate B-cell migration; probably by forming a heterodimer with CXCR5 that affects the interaction between of CXCL13 and CXCR5 (PubMed:22913878). Also acts as a chemotactic receptor for some T-cells upon binding to 7-alpha,25-OHC ligand (By similarity). Promotes follicular helper T (Tfh) cells differentiation by positioning activated T-cells at the follicle-T-zone interface, promoting contact of newly activated CD4 T-cells with activated dendritic cells and exposing them to Tfh-cell-promoting inducible costimulator (ICOS) ligand (By similarity). Expression in splenic dendritic cells is required for their homeostasis, localization and ability to induce B- and T-cell responses: GPR183 acts as a chemotactic receptor in dendritic cells that mediates the accumulation of CD4(+) dendritic cells in bridging channels (By similarity). Regulates migration of astrocytes and is involved in communication between astrocytes and macrophages (PubMed:25297897). Promotes osteoclast precursor migration to bone surfaces (By similarity). Signals constitutively through G(i)-alpha, but not G(s)-alpha or G(q)-alpha (PubMed:21673108, PubMed:25297897). Signals constitutively also via MAPK1/3 (ERK1/2) (By similarity).[UniProtKB:Q3U6B2]<ref>PMID:16540462</ref> <ref>PMID:21673108</ref> <ref>PMID:21796212</ref> <ref>PMID:22875855</ref> <ref>PMID:22913878</ref> <ref>PMID:22930711</ref> <ref>PMID:25297897</ref>
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[https://www.uniprot.org/uniprot/GP183_HUMAN GP183_HUMAN] G-protein coupled receptor expressed in lymphocytes that acts as a chemotactic receptor for B-cells, T-cells, splenic dendritic cells, monocytes/macrophages and astrocytes (By similarity). Receptor for oxysterol 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC) and other related oxysterols (PubMed:21796212, PubMed:22875855, PubMed:22930711). Mediates cell positioning and movement of a number of cells by binding the 7-alpha,25-OHC ligand that forms a chemotactic gradient (By similarity). Binding of 7-alpha,25-OHC mediates the correct localization of B-cells during humoral immune responses (By similarity). Guides B-cell movement along the B-cell zone-T-cell zone boundary and later to interfollicular and outer follicular regions (By similarity). Its specific expression during B-cell maturation helps position B-cells appropriately for mounting T-dependent antibody responses (By similarity). Collaborates with CXCR5 to mediate B-cell migration; probably by forming a heterodimer with CXCR5 that affects the interaction between of CXCL13 and CXCR5 (PubMed:22913878). Also acts as a chemotactic receptor for some T-cells upon binding to 7-alpha,25-OHC ligand (By similarity). Promotes follicular helper T (Tfh) cells differentiation by positioning activated T-cells at the follicle-T-zone interface, promoting contact of newly activated CD4 T-cells with activated dendritic cells and exposing them to Tfh-cell-promoting inducible costimulator (ICOS) ligand (By similarity). Expression in splenic dendritic cells is required for their homeostasis, localization and ability to induce B- and T-cell responses: GPR183 acts as a chemotactic receptor in dendritic cells that mediates the accumulation of CD4(+) dendritic cells in bridging channels (By similarity). Regulates migration of astrocytes and is involved in communication between astrocytes and macrophages (PubMed:25297897). Promotes osteoclast precursor migration to bone surfaces (By similarity). Signals constitutively through G(i)-alpha, but not G(s)-alpha or G(q)-alpha (PubMed:21673108, PubMed:25297897). Signals constitutively also via MAPK1/3 (ERK1/2) (By similarity).[UniProtKB:Q3U6B2]<ref>PMID:16540462</ref> <ref>PMID:21673108</ref> <ref>PMID:21796212</ref> <ref>PMID:22875855</ref> <ref>PMID:22913878</ref> <ref>PMID:22930711</ref> <ref>PMID:25297897</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Oxysterols induce the migration of B-lymphocytes and dendritic cells to interfollicular regions of lymphoid tissues through binding the EBI2 (GPR183) to stimulate effective adaptive immunity and antibody production during infection. Aberrant EBI2 signaling is implicated in inflammatory bowel disease, sclerosis, and infectious disease. Here, we report the cryo-EM structures of an EBI2-G(i) signaling complex with its endogenous agonist 7alpha,25-OHC and that of an inactive EBI2 bound to the inverse agonist GSK682753A. These structures reveal an agonist binding site for the oxysterol and a potential ligand entrance site exposed to the lipid bilayer. Mutations within the oxysterol binding site and the Galpha(i) interface attenuate G protein signaling and abolish oxysterol-mediated cell migration indicating that G protein signaling directly involves in the oxysterol-EBI2 pathway. Together, these findings provide new insight into how EBI2 is activated by an oxysterol ligand and will facilitate the development of therapeutic approaches that target EBI2-linked diseases.
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, PMID:35537452<ref>PMID:35537452</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 7tuy" style="background-color:#fffaf0;"></div>
== References ==
== References ==
<references/>
<references/>

Current revision

Cryo-EM structure of GSK682753A-bound EBI2/GPR183

PDB ID 7tuy

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