[English] 日本語
Yorodumi
- PDB-8hnm: CXCR3-DNGi complex activated by VUF11222 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8hnm
TitleCXCR3-DNGi complex activated by VUF11222
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Soluble cytochrome b562,C-X-C chemokine receptor type 3,Oplophorus-luciferin 2-monooxygenase catalytic subunit
  • single-chain variable fragment scFv16
KeywordsSIGNALING PROTEIN / G protein coupled receptor / chemokine receptor / CXCR3 / VUF11222 / complex
Function / homology
Function and homology information


Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / regulation of leukocyte migration / C-X-C chemokine binding / chemokine binding / C-X-C chemokine receptor activity / chemokine receptor activity / C-C chemokine receptor activity / C-C chemokine binding / positive regulation of chemotaxis ...Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / regulation of leukocyte migration / C-X-C chemokine binding / chemokine binding / C-X-C chemokine receptor activity / chemokine receptor activity / C-C chemokine receptor activity / C-C chemokine binding / positive regulation of chemotaxis / negative regulation of execution phase of apoptosis / Chemokine receptors bind chemokines / negative regulation of endothelial cell proliferation / positive regulation of execution phase of apoptosis / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cell adhesion / regulation of cAMP-mediated signaling / G protein-coupled serotonin receptor binding / cellular response to forskolin / regulation of mitotic spindle organization / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / negative regulation of angiogenesis / bioluminescence / cell chemotaxis / positive regulation of release of sequestered calcium ion into cytosol / Regulation of insulin secretion / G protein-coupled receptor binding / calcium-mediated signaling / electron transport chain / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / response to peptide hormone / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / positive regulation of angiogenesis / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / chemotaxis / GPER1 signaling / GDP binding / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / signaling receptor activity / Ca2+ pathway / cell cortex / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement / G alpha (q) signalling events / angiogenesis / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / periplasmic space / electron transfer activity / cell surface receptor signaling pathway / cell adhesion / inflammatory response / immune response
Similarity search - Function
CXC chemokine receptor 3 / Chemokine receptor family / : / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / G-protein alpha subunit, group I / Calycin / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion ...CXC chemokine receptor 3 / Chemokine receptor family / : / Cytochrome b562 / Cytochrome b562 / Cytochrome c/b562 / G-protein alpha subunit, group I / Calycin / 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 / 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. / WD domain, G-beta repeat / 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
Chem-4IE / CHOLESTEROL / Soluble cytochrome b562 / C-X-C chemokine receptor type 3 / 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 / Oplophorus-luciferin 2-monooxygenase catalytic subunit
Similarity search - Component
Biological speciesHomo sapiens (human)
Escherichia coli (E. coli)
Oplophorus gracilirostris (crustacean)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.94 Å
AuthorsJiao, H.Z. / Hu, H.L.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32100963 China
CitationJournal: Nat Struct Mol Biol / Year: 2024
Title: Structural insights into the activation and inhibition of CXC chemokine receptor 3.
Authors: Haizhan Jiao / Bin Pang / Aijun Liu / Qiang Chen / Qi Pan / Xiankun Wang / Yunong Xu / Ying-Chih Chiang / Ruobing Ren / Hongli Hu /
Abstract: The chemotaxis of CD4 type 1 helper cells and CD8 cytotoxic lymphocytes, guided by interferon-inducible CXC chemokine 9-11 (CXCL9-11) and CXC chemokine receptor 3 (CXCR3), plays a critical role in ...The chemotaxis of CD4 type 1 helper cells and CD8 cytotoxic lymphocytes, guided by interferon-inducible CXC chemokine 9-11 (CXCL9-11) and CXC chemokine receptor 3 (CXCR3), plays a critical role in type 1 immunity. Here we determined the structures of human CXCR3-DNG complexes activated by chemokine CXCL11, peptidomimetic agonist PS372424 and biaryl-type agonist VUF11222, and the structure of inactive CXCR3 bound to noncompetitive antagonist SCH546738. Structural analysis revealed that PS372424 shares a similar orthosteric binding pocket to the N terminus of CXCL11, while VUF11222 buries deeper and activates the receptor in a distinct manner. We showed an allosteric binding site between TM5 and TM6, accommodating SCH546738 in the inactive CXCR3. SCH546738 may restrain the receptor at an inactive state by preventing the repacking of TM5 and TM6. By revealing the binding patterns and the pharmacological properties of the four modulators, we present the activation mechanisms of CXCR3 and provide insights for future drug development.
History
DepositionDec 8, 2022Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Nov 29, 2023Provider: repository / Type: Initial release
Revision 1.1Jan 17, 2024Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation.title ..._citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.name
Revision 1.2May 1, 2024Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Guanine nucleotide-binding protein G(i) subunit alpha-1
B: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
G: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
R: Soluble cytochrome b562,C-X-C chemokine receptor type 3,Oplophorus-luciferin 2-monooxygenase catalytic subunit
S: single-chain variable fragment scFv16
hetero molecules


Theoretical massNumber of molelcules
Total (without water)192,2148
Polymers191,0155
Non-polymers1,1993
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

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

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


Mass: 40445.059 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
#2: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 42005.895 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

-
Protein / Antibody , 2 types, 2 molecules RS

#4: Protein Soluble cytochrome b562,C-X-C chemokine receptor type 3,Oplophorus-luciferin 2-monooxygenase catalytic subunit / Cytochrome b-562 / CXC-R3 / CXCR-3 / CKR-L2 / G protein-coupled receptor 9 / Interferon-inducible ...Cytochrome b-562 / CXC-R3 / CXCR-3 / CKR-L2 / G protein-coupled receptor 9 / Interferon-inducible protein 10 receptor / IP-10 receptor / 19kOLase


Mass: 72918.008 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Escherichia coli (E. coli), (gene. exp.) Homo sapiens (human), (gene. exp.) Oplophorus gracilirostris (crustacean)
Gene: cybC, CXCR3, GPR9 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P0ABE7, UniProt: P49682, UniProt: Q9GV45, Oplophorus-luciferin 2-monooxygenase
#5: Antibody single-chain variable fragment scFv16


Mass: 27784.896 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Spodoptera frugiperda (fall armyworm)

-
Non-polymers , 2 types, 3 molecules

#6: Chemical ChemComp-CLR / CHOLESTEROL


Mass: 386.654 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H46O
#7: Chemical ChemComp-4IE / [4-(2-bromophenyl)phenyl]methyl-[[(1R,5S)-6,6-dimethyl-2-bicyclo[3.1.1]hept-2-enyl]methyl]-dimethyl-azanium / VUF11222


Mass: 425.424 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C25H31BrN / Feature type: SUBJECT OF INVESTIGATION

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

ComponentName: CXCR3-VUF11222-DNGi-scFv16 / Type: COMPLEX / Entity ID: #1-#5 / Source: MULTIPLE SOURCES
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 7.5
SpecimenConc.: 5 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE / Humidity: 100 %

-
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 magnification: 105000 X / Nominal defocus max: 1800 nm / Nominal defocus min: 1200 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm
Image recordingElectron dose: 54.31 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k)
EM imaging opticsEnergyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV

-
Processing

SoftwareName: PHENIX / Version: 1.20.1_4487: / Classification: refinement
EM softwareName: Gctf / Category: CTF correction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.94 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 162856 / Symmetry type: POINT
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0038968
ELECTRON MICROSCOPYf_angle_d0.6312163
ELECTRON MICROSCOPYf_dihedral_angle_d51254
ELECTRON MICROSCOPYf_chiral_restr0.0441393
ELECTRON MICROSCOPYf_plane_restr0.0041527

+
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