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Open data
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Basic information
Entry | Database: PDB / ID: 8u4t | |||||||||||||||||||||||||||||||||||||||||||||
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Title | Structure of tetrameric CXCR4 in complex with REGN7663 Fab | |||||||||||||||||||||||||||||||||||||||||||||
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![]() | SIGNALING PROTEIN/IMMUNE SYSTEM / GPCR / chemokine receptor / tetramer / oligomer / antibody / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||||||||||||||||||||||||||||||||
Function / homology | ![]() C-X-C motif chemokine 12 receptor activity / positive regulation of macrophage migration inhibitory factor signaling pathway / Specification of primordial germ cells / CXCL12-activated CXCR4 signaling pathway / myosin light chain binding / myelin maintenance / C-X-C chemokine receptor activity / positive regulation of vasculature development / Signaling by ROBO receptors / regulation of chemotaxis ...C-X-C motif chemokine 12 receptor activity / positive regulation of macrophage migration inhibitory factor signaling pathway / Specification of primordial germ cells / CXCL12-activated CXCR4 signaling pathway / myosin light chain binding / myelin maintenance / C-X-C chemokine receptor activity / positive regulation of vasculature development / Signaling by ROBO receptors / regulation of chemotaxis / Formation of definitive endoderm / C-C chemokine receptor activity / C-C chemokine binding / Developmental Lineage of Pancreatic Acinar Cells / Chemokine receptors bind chemokines / anchoring junction / dendritic cell chemotaxis / cellular response to cytokine stimulus / cell leading edge / positive regulation of oligodendrocyte differentiation / Binding and entry of HIV virion / regulation of cell adhesion / coreceptor activity / neurogenesis / ubiquitin binding / cell chemotaxis / calcium-mediated signaling / G protein-coupled receptor activity / brain development / response to virus / late endosome / actin binding / positive regulation of cold-induced thermogenesis / virus receptor activity / positive regulation of cytosolic calcium ion concentration / cytoplasmic vesicle / G alpha (i) signalling events / response to hypoxia / early endosome / lysosome / immune response / positive regulation of cell migration / G protein-coupled receptor signaling pathway / inflammatory response / external side of plasma membrane / ubiquitin protein ligase binding / apoptotic process / cell surface / protein-containing complex / extracellular exosome / plasma membrane / cytoplasm Similarity search - Function | |||||||||||||||||||||||||||||||||||||||||||||
Biological species | ![]() | |||||||||||||||||||||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.38 Å | |||||||||||||||||||||||||||||||||||||||||||||
![]() | Saotome, K. / McGoldrick, L.L. / Franklin, M.C. | |||||||||||||||||||||||||||||||||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into CXCR4 modulation and oligomerization. Authors: Kei Saotome / Luke L McGoldrick / Jo-Hao Ho / Trudy F Ramlall / Sweta Shah / Michael J Moore / Jee Hae Kim / Raymond Leidich / William C Olson / Matthew C Franklin / ![]() Abstract: Activation of the chemokine receptor CXCR4 by its chemokine ligand CXCL12 regulates diverse cellular processes. Previously reported crystal structures of CXCR4 revealed the architecture of an ...Activation of the chemokine receptor CXCR4 by its chemokine ligand CXCL12 regulates diverse cellular processes. Previously reported crystal structures of CXCR4 revealed the architecture of an inactive, homodimeric receptor. However, many structural aspects of CXCR4 remain poorly understood. Here, we use cryo-electron microscopy to investigate various modes of human CXCR4 regulation. CXCL12 activates CXCR4 by inserting its N terminus deep into the CXCR4 orthosteric pocket. The binding of US Food and Drug Administration-approved antagonist AMD3100 is stabilized by electrostatic interactions with acidic residues in the seven-transmembrane-helix bundle. A potent antibody blocker, REGN7663, binds across the extracellular face of CXCR4 and inserts its complementarity-determining region H3 loop into the orthosteric pocket. Trimeric and tetrameric structures of CXCR4 reveal modes of G-protein-coupled receptor oligomerization. We show that CXCR4 adopts distinct subunit conformations in trimeric and tetrameric assemblies, highlighting how oligomerization could allosterically regulate chemokine receptor function. #1: ![]() Title: Structural insights into CXCR4 modulation and oligomerization Authors: Saotome, K. / McGoldrick, L.L. / Ho, J. / Ramlall, T. / Shah, S. / Moore, M.J. / Kim, J.H. / Leidich, R. / Olson, W.C. / Franklin, M.C. | |||||||||||||||||||||||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 492.5 KB | Display | ![]() |
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PDB format | ![]() | Display | ![]() | |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
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-Validation report
Summary document | ![]() | 2.5 MB | Display | ![]() |
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Full document | ![]() | 2.5 MB | Display | |
Data in XML | ![]() | 71.6 KB | Display | |
Data in CIF | ![]() | 100.5 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 41894MC ![]() 8u4nC ![]() 8u4oC ![]() 8u4pC ![]() 8u4qC ![]() 8u4rC ![]() 8u4sC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Assembly
Deposited unit | ![]()
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Noncrystallographic symmetry (NCS) | NCS domain:
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