[English] 日本語
Yorodumi
- PDB-8k3z: Cryo-EM structure of CXCR4 in complex with CXCL12 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8k3z
TitleCryo-EM structure of CXCR4 in complex with CXCL12
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • C-X-C chemokine receptor type 4
  • Stromal cell-derived factor 1
  • scFv16
KeywordsIMMUNE SYSTEM / Chemokine receptor / CXCR4
Function / homology
Function and homology information


telencephalon cell migration / chemokine (C-X-C motif) ligand 12 signaling pathway / C-X-C motif chemokine 12 receptor activity / response to ultrasound / negative regulation of leukocyte tethering or rolling / positive regulation of macrophage migration inhibitory factor signaling pathway / regulation of actin polymerization or depolymerization / chemokine receptor binding / Specification of primordial germ cells / CXCL12-activated CXCR4 signaling pathway ...telencephalon cell migration / chemokine (C-X-C motif) ligand 12 signaling pathway / C-X-C motif chemokine 12 receptor activity / response to ultrasound / negative regulation of leukocyte tethering or rolling / positive regulation of macrophage migration inhibitory factor signaling pathway / regulation of actin polymerization or depolymerization / chemokine receptor binding / Specification of primordial germ cells / CXCL12-activated CXCR4 signaling pathway / myosin light chain binding / myelin maintenance / CXCR chemokine receptor binding / C-X-C chemokine receptor activity / positive regulation of axon extension involved in axon guidance / positive regulation of vasculature development / positive regulation of dopamine secretion / Signaling by ROBO receptors / regulation of chemotaxis / induction of positive chemotaxis / Formation of definitive endoderm / integrin activation / negative regulation of dendritic cell apoptotic process / negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage / C-C chemokine receptor activity / cellular response to chemokine / chemokine-mediated signaling pathway / Developmental Lineage of Pancreatic Acinar Cells / C-C chemokine binding / positive regulation of monocyte chemotaxis / chemokine activity / blood circulation / Chemokine receptors bind chemokines / anchoring junction / dendritic cell chemotaxis / positive regulation of calcium ion import / cellular response to cytokine stimulus / detection of temperature stimulus involved in sensory perception of pain / cell leading edge / positive regulation of oligodendrocyte differentiation / animal organ regeneration / Binding and entry of HIV virion / detection of mechanical stimulus involved in sensory perception of pain / positive regulation of T cell migration / regulation of cell adhesion / Nuclear signaling by ERBB4 / adenylate cyclase inhibitor activity / coreceptor activity / positive regulation of protein localization to cell cortex / T cell migration / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / response to prostaglandin E / positive regulation of endothelial cell proliferation / neurogenesis / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / positive regulation of neuron differentiation / positive regulation of cell adhesion / cellular response to forskolin / axon guidance / regulation of mitotic spindle organization / ubiquitin binding / adult locomotory behavior / cell chemotaxis / growth factor activity / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / calcium-mediated signaling / defense response / negative regulation of insulin secretion / G protein-coupled receptor binding / response to peptide hormone / brain development / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to virus / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / centriolar satellite / integrin binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / neuron migration / Activation of the phototransduction cascade / intracellular calcium ion homeostasis / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / chemotaxis / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12
Similarity search - Function
CXC chemokine receptor 4 N-terminal domain / CXCR4 Chemokine receptor N terminal / CXC chemokine receptor 4/atypical chemokine receptor 2 / CXC Chemokine domain / Chemokine receptor family / : / Chemokine beta/gamma/delta / Intercrine alpha family (small cytokine C-X-C) (chemokine CXC). / Chemokine interleukin-8-like domain / Chemokine interleukin-8-like superfamily ...CXC chemokine receptor 4 N-terminal domain / CXCR4 Chemokine receptor N terminal / CXC chemokine receptor 4/atypical chemokine receptor 2 / CXC Chemokine domain / Chemokine receptor family / : / Chemokine beta/gamma/delta / Intercrine alpha family (small cytokine C-X-C) (chemokine CXC). / Chemokine interleukin-8-like domain / Chemokine interleukin-8-like superfamily / Small cytokines (intecrine/chemokine), interleukin-8 like / G-protein alpha subunit, group I / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G-alpha domain profile. / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / G-protein gamma-like domain / G-protein gamma-like domain superfamily / GGL domain / G protein gamma subunit-like motifs / GGL domain / G protein beta WD-40 repeat protein / Guanine nucleotide-binding protein, beta subunit / G-protein, beta subunit / G-protein coupled receptors family 1 signature. / G protein-coupled receptor, rhodopsin-like / GPCR, rhodopsin-like, 7TM / G-protein coupled receptors family 1 profile. / 7 transmembrane receptor (rhodopsin family) / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / P-loop containing nucleoside triphosphate hydrolase
Similarity search - Domain/homology
Stromal cell-derived factor 1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / C-X-C chemokine receptor type 4 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1
Similarity search - Component
Biological speciesHomo sapiens (human)
Vicugna pacos (alpaca)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.81 Å
AuthorsLiu, Y.Z. / Liu, A.J. / Liao, Q.W. / Ye, R.D.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: Cell Rep / Year: 2024
Title: Cryo-EM structure of monomeric CXCL12-bound CXCR4 in the active state.
Authors: Yezhou Liu / Aijun Liu / Xinyu Li / Qiwen Liao / Weijia Zhang / Lizhe Zhu / Richard D Ye /
Abstract: CXCR4 binding of its endogenous agonist CXCL12 leads to diverse functions, including bone marrow retention of hematopoietic progenitors and cancer metastasis. However, the structure of the CXCL12- ...CXCR4 binding of its endogenous agonist CXCL12 leads to diverse functions, including bone marrow retention of hematopoietic progenitors and cancer metastasis. However, the structure of the CXCL12-bound CXCR4 remains unresolved despite available structures of CXCR4 in complex with antagonists. Here, we present the cryoelectron microscopy (cryo-EM) structure of the CXCL12-CXCR4-Gi complex at an overall resolution of 2.65 Å. CXCL12 forms a 1:1 stoichiometry complex with CXCR4, following the two-site model. The first 8 amino acids of mature CXCL12 are crucial for CXCR4 activation by forming polar interactions with minor sub-pocket residues in the transmembrane binding pocket. The 3.2-Å distance between V3 of CXCL12 and the "toggle switch" W marks the deepest insertion among all chemokine-receptor pairs, leading to conformational changes of CXCR4 for G protein activation. These results, combined with functional assays and computational analysis, provide the structural basis for CXCR4 activation by CXCL12.
History
DepositionJul 17, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jul 17, 2024Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: FSC / Data content type: FSC / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jul 17, 2024Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Nov 13, 2024Group: Data collection / Structure summary
Category: em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update
Revision 1.2Jan 29, 2025Group: Data collection / Database references / Category: citation / citation_author / em_admin
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _em_admin.last_update
Revision 1.3Jul 2, 2025Group: Data collection / Category: em_admin / em_software / Item: _em_admin.last_update / _em_software.name
Revision 1.1Jul 2, 2025Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Data processing / Experimental summary / Data content type: EM metadata / EM metadata / Category: em_admin / em_software / Data content type: EM metadata / EM metadata / Item: _em_admin.last_update / _em_software.name

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: C-X-C chemokine receptor type 4
B: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
C: Guanine nucleotide-binding protein G(i) subunit alpha-1
D: Stromal cell-derived factor 1
G: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
S: scFv16


Theoretical massNumber of molelcules
Total (without water)151,2016
Polymers151,2016
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

-
Components

-
Protein , 2 types, 2 molecules AD

#1: Protein C-X-C chemokine receptor type 4 / CXC-R4 / CXCR-4 / FB22 / Fusin / HM89 / LCR1 / Leukocyte-derived seven transmembrane domain ...CXC-R4 / CXCR-4 / FB22 / Fusin / HM89 / LCR1 / Leukocyte-derived seven transmembrane domain receptor / LESTR / Lipopolysaccharide-associated protein 3 / LAP-3 / LPS-associated protein 3 / NPYRL / Stromal cell-derived factor 1 receptor / SDF-1 receptor


Mass: 33826.059 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CXCR4 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P61073
#4: Protein Stromal cell-derived factor 1 / SDF-1 / hSDF-1 / C-X-C motif chemokine 12 / Intercrine reduced in hepatomas / IRH / hIRH / Pre-B ...SDF-1 / hSDF-1 / C-X-C motif chemokine 12 / Intercrine reduced in hepatomas / IRH / hIRH / Pre-B cell growth-stimulating factor / PBSF


Mass: 7292.648 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CXCL12, SDF1, SDF1A, SDF1B / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P48061

-
Guanine nucleotide-binding protein ... , 3 types, 3 molecules BCG

#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 37198.656 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62873
#3: Protein Guanine nucleotide-binding protein G(i) subunit alpha-1 / Adenylate cyclase-inhibiting G alpha protein


Mass: 40415.031 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63096
#5: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 6131.084 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P59768

-
Antibody , 1 types, 1 molecules S

#6: Antibody scFv16


Mass: 26337.307 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Vicugna pacos (alpaca) / Production host: Spodoptera frugiperda (fall armyworm)

-
Details

Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: CXCR4-CXCL12-Gi-scFv16 complex / Type: COMPLEX / Entity ID: #6, #5, #2-#3, #1, #4 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2500 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

EM softwareName: PHENIX / Category: model refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.81 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 373108 / Symmetry type: POINT

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more