[English] 日本語
Yorodumi
- PDB-7xbx: Cryo-EM structure of the human chemokine receptor CX3CR1 in compl... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7xbx
TitleCryo-EM structure of the human chemokine receptor CX3CR1 in complex with CX3CL1 and Gi1
Components
  • Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
  • Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
  • Guanine nucleotide-binding protein G(i) subunit alpha-1
  • Processed fractalkine,CX3C chemokine receptor 1
KeywordsSIGNALING PROTEIN / G protein-coupled receptor / chemokine receptor / CX3CR1 / CX3CL1
Function / homology
Function and homology information


C-X3-C chemokine receptor activity / dendritic tree / multiple spine synapse organization, single dendrite / negative regulation of microglial cell mediated cytotoxicity / macropinosome membrane / C-X3-C chemokine binding / regulation of microglial cell migration / CXCR1 chemokine receptor binding / positive regulation of calcium-independent cell-cell adhesion / negative regulation of interleukin-1 alpha production ...C-X3-C chemokine receptor activity / dendritic tree / multiple spine synapse organization, single dendrite / negative regulation of microglial cell mediated cytotoxicity / macropinosome membrane / C-X3-C chemokine binding / regulation of microglial cell migration / CXCR1 chemokine receptor binding / positive regulation of calcium-independent cell-cell adhesion / negative regulation of interleukin-1 alpha production / leukocyte adhesive activation / CX3C chemokine receptor binding / negative regulation of glutamate receptor signaling pathway / microglial cell activation involved in immune response / autocrine signaling / host-mediated modulation of intestinal microbiota composition / lymphocyte chemotaxis / synapse pruning / positive regulation of microglial cell migration / regulation of lipopolysaccharide-mediated signaling pathway / central nervous system maturation / negative regulation of microglial cell activation / synapse maturation / negative regulation of neuron migration / negative regulation of hippocampal neuron apoptotic process / antifungal innate immune response / positive regulation of transforming growth factor beta1 production / chemokine receptor activity / CCR chemokine receptor binding / microglial cell proliferation / positive regulation of actin filament bundle assembly / leukocyte migration involved in inflammatory response / integrin activation / leukocyte tethering or rolling / regulation of tumor necrosis factor production / C-C chemokine receptor activity / chemokine-mediated signaling pathway / eosinophil chemotaxis / C-C chemokine binding / positive regulation of monocyte chemotaxis / leukocyte chemotaxis / G protein-coupled peptide receptor activity / regulation of nitric oxide biosynthetic process / angiogenesis involved in wound healing / chemokine activity / positive regulation of neurogenesis / Chemokine receptors bind chemokines / negative regulation of interleukin-1 beta production / positive regulation of cell-matrix adhesion / neuronal cell body membrane / neuron remodeling / positive regulation of neuroblast proliferation / positive chemotaxis / chemoattractant activity / RSV-host interactions / macrophage chemotaxis / negative regulation of interleukin-6 production / Respiratory syncytial virus (RSV) attachment and entry / negative regulation of apoptotic signaling pathway / negative regulation of tumor necrosis factor production / social behavior / negative regulation of cell-substrate adhesion / regulation of neurogenesis / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / cellular defense response / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / neutrophil chemotaxis / adenylate cyclase-inhibiting serotonin receptor signaling pathway / extrinsic apoptotic signaling pathway in absence of ligand / positive regulation of smooth muscle cell proliferation / cellular response to forskolin / regulation of mitotic spindle organization / negative regulation of cell migration / negative regulation of angiogenesis / positive regulation of release of sequestered calcium ion into cytosol / response to ischemia / cell chemotaxis / cell projection / Regulation of insulin secretion / calcium-mediated signaling / positive regulation of cholesterol biosynthetic process / microglial cell activation / negative regulation of insulin secretion / defense response / cell-cell adhesion / G protein-coupled receptor binding / positive regulation of neuron projection development / G protein-coupled receptor activity / response to peptide hormone / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / neuron cellular homeostasis / brain development / modulation of chemical synaptic transmission
Similarity search - Function
CX3C chemokine receptor 1 / CX3C chemokine domain / : / 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 ...CX3C chemokine receptor 1 / CX3C chemokine domain / : / 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
CHOLESTEROL / CX3C chemokine receptor 1 / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(i) subunit alpha-1 / Fractalkine
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å
AuthorsLu, M. / Zhao, W. / Han, S. / Zhu, Y. / Wu, B. / Zhao, Q.
Funding support China, 3items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)31825010 China
National Natural Science Foundation of China (NSFC)82121005 China
National Natural Science Foundation of China (NSFC)31800618 China
CitationJournal: Sci Adv / Year: 2022
Title: Activation of the human chemokine receptor CX3CR1 regulated by cholesterol.
Authors: Minmin Lu / Wenli Zhao / Shuo Han / Xiaowen Lin / Tingyu Xu / Qiuxiang Tan / Mu Wang / Cuiying Yi / Xiaojing Chu / Weibo Yang / Ya Zhu / Beili Wu / Qiang Zhao /
Abstract: As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand CX3CL1, which shows notable potential as a therapeutic target in atherosclerosis, cancer, and ...As the only member of the CX3C chemokine receptor subfamily, CX3CR1 binds to its sole endogenous ligand CX3CL1, which shows notable potential as a therapeutic target in atherosclerosis, cancer, and neuropathy. However, the drug development of CX3CR1 is hampered partially by the lack of structural information. Here, we present two cryo-electron microscopy structures of CX3CR1-G complexes in ligand-free and CX3CL1-bound states at 2.8- and 3.4-Å resolution, respectively. Together with functional data, the structures reveal the key factors that govern the recognition of CX3CL1 by both CX3CR1 and US28. A much smaller conformational change of helix VI upon activation than previously solved class A GPCR-G complex structures is observed in CX3CR1, which may correlate with three cholesterol molecules that play essential roles in conformation stabilization and signaling transduction. Thus, our data deepen the understanding of cholesterol modulation in GPCR (G protein-coupled receptor) signaling and provide insights into the diversity of G protein coupling.
History
DepositionMar 22, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Jul 13, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 30, 2024Group: Data collection / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / em_admin / pdbx_entry_details / pdbx_modification_feature
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
C: Guanine nucleotide-binding protein G(i) subunit alpha-1
D: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
E: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
R: Processed fractalkine,CX3C chemokine receptor 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)138,8866
Polymers138,1124
Non-polymers7732
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

#1: Protein Guanine nucleotide-binding protein G(i) subunit alpha-1 / Adenylate cyclase-inhibiting G alpha protein


Mass: 40447.141 Da / Num. of mol.: 1 / Mutation: S47C,G202T,G203A,E245A,A326S
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
#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 38245.805 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)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 7861.143 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
#4: Protein Processed fractalkine,CX3C chemokine receptor 1 / C-X3-C CKR-1 / CX3CR1 / Beta chemokine receptor-like 1 / CMK-BRL-1 / CMK-BRL1 / Fractalkine ...C-X3-C CKR-1 / CX3CR1 / Beta chemokine receptor-like 1 / CMK-BRL-1 / CMK-BRL1 / Fractalkine receptor / G-protein coupled receptor 13 / V28


Mass: 51558.250 Da / Num. of mol.: 1 / Mutation: G35C,I222L,L278C,C323S,M352V
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CX3CR1, CMKBRL1, GPR13 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P78423, UniProt: P49238
#5: Chemical ChemComp-CLR / CHOLESTEROL


Mass: 386.654 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H46O
Has ligand of interestN
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: Chemokine receptor CX3CR1 in complex with CX3CL1 Gi1 / Type: COMPLEX / Entity ID: #1-#4 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
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: SPOT SCAN
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 800 nm
Image recordingElectron dose: 2.1875 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)

-
Processing

Software
NameVersionClassification
phenix.real_space_refine1.18.2_3874refinement
PHENIX1.18.2_3874refinement
CTF correctionType: NONE
3D reconstructionResolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 490779 / Symmetry type: POINT
RefinementCross valid method: NONE
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
Displacement parametersBiso mean: 92.34 Å2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00186754
ELECTRON MICROSCOPYf_angle_d0.43649252
ELECTRON MICROSCOPYf_chiral_restr0.03731143
ELECTRON MICROSCOPYf_plane_restr0.00241155
ELECTRON MICROSCOPYf_dihedral_angle_d4.0931960

+
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