+
Open data
-
Basic information
Entry | Database: PDB / ID: 7vl9 | ||||||
---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of the CCL15(26-92) bound CCR1-Gi complex | ||||||
![]() |
| ||||||
![]() | MEMBRANE PROTEIN / GPCR / CCR1 / Chemokine Receptor / MEMBRNE PROTEIN | ||||||
Function / homology | ![]() chemokine (C-C motif) ligand 7 binding / chemokine (C-C motif) ligand 5 binding / chemokine receptor activity / negative regulation of bone mineralization / CCR chemokine receptor binding / C-C chemokine receptor activity / C-C chemokine binding / phosphatidylinositol phospholipase C activity / positive regulation of calcium ion transport / eosinophil chemotaxis ...chemokine (C-C motif) ligand 7 binding / chemokine (C-C motif) ligand 5 binding / chemokine receptor activity / negative regulation of bone mineralization / CCR chemokine receptor binding / C-C chemokine receptor activity / C-C chemokine binding / phosphatidylinositol phospholipase C activity / positive regulation of calcium ion transport / eosinophil chemotaxis / positive regulation of osteoclast differentiation / positive regulation of monocyte chemotaxis / chemokine-mediated signaling pathway / Chemokine receptors bind chemokines / chemokine activity / dendritic cell chemotaxis / chemoattractant activity / exocytosis / monocyte chemotaxis / Interleukin-10 signaling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / regulation of mitotic spindle organization / cellular response to forskolin / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / cell chemotaxis / Regulation of insulin secretion / G protein-coupled receptor binding / calcium-mediated signaling / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating 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 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / cytokine-mediated signaling pathway / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / response to wounding / Vasopressin regulates renal water homeostasis via Aquaporins / intracellular calcium ion homeostasis / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / GDP binding / chemotaxis / G-protein beta-subunit binding / calcium ion transport / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / antimicrobial humoral immune response mediated by antimicrobial peptide / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / cell-cell signaling / retina development in camera-type eye / Ca2+ pathway / heparin binding / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cell cortex / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade / cell surface receptor signaling pathway / cell adhesion Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.6 Å | ||||||
![]() | Shao, Z. / Shen, Q. / Mao, C. / Yao, B. / Chen, L. / Zhang, H. / Shen, D. / Zhang, C. / Li, W. / Du, X. ...Shao, Z. / Shen, Q. / Mao, C. / Yao, B. / Chen, L. / Zhang, H. / Shen, D. / Zhang, C. / Li, W. / Du, X. / Li, F. / Ma, H. / Chen, Z. / Xu, H.E. / Ying, S. / Zhang, Y. / Shen, H. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1. Authors: Zhehua Shao / Qingya Shen / Bingpeng Yao / Chunyou Mao / Li-Nan Chen / Huibing Zhang / Dan-Dan Shen / Chao Zhang / Weijie Li / Xufei Du / Fei Li / Honglei Ma / Zhi-Hua Chen / H Eric Xu / ...Authors: Zhehua Shao / Qingya Shen / Bingpeng Yao / Chunyou Mao / Li-Nan Chen / Huibing Zhang / Dan-Dan Shen / Chao Zhang / Weijie Li / Xufei Du / Fei Li / Honglei Ma / Zhi-Hua Chen / H Eric Xu / Songmin Ying / Yan Zhang / Huahao Shen / ![]() Abstract: Biased signaling of G protein-coupled receptors describes an ability of different ligands that preferentially activate an alternative downstream signaling pathway. In this work, we identified and ...Biased signaling of G protein-coupled receptors describes an ability of different ligands that preferentially activate an alternative downstream signaling pathway. In this work, we identified and characterized different N-terminal truncations of endogenous chemokine CCL15 as balanced or biased agonists targeting CCR1, and presented three cryogenic-electron microscopy structures of the CCR1-G complex in the ligand-free form or bound to different CCL15 truncations with a resolution of 2.6-2.9 Å, illustrating the structural basis of natural biased signaling that initiates an inflammation response. Complemented with pharmacological and computational studies, these structures revealed it was the conformational change of Tyr291 (Y291) in CCR1 that triggered its polar network rearrangement in the orthosteric binding pocket and allosterically regulated the activation of β-arrestin signaling. Our structure of CCL15-bound CCR1 also exhibited a critical site for ligand binding distinct from many other chemokine-receptor complexes, providing new insights into the mode of chemokine recognition. | ||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 230.8 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 181 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 32021MC ![]() 7vl8C ![]() 7vlaC M: map data used to model this data C: citing same article ( |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#1: Protein | Mass: 40414.047 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
---|---|
#2: Protein | Mass: 37728.152 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Protein , 2 types, 2 molecules LR
#4: Protein | Mass: 8365.681 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
---|---|
#5: Protein | Mass: 42203.547 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
-Antibody / Non-polymers , 2 types, 2 molecules S![](data/chem/img/CLR.gif)
![](data/chem/img/CLR.gif)
#6: Antibody | Mass: 27340.482 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
---|---|
#7: Chemical | ChemComp-CLR / |
-Details
Has ligand of interest | Y |
---|
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-
Sample preparation
Component | Name: CCL15(26-92)-bound CCR1-Gi complex / Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD |
Image recording | Electron dose: 62 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K3 (6k x 4k) |
-
Processing
Software |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EM software |
| ||||||||||||||||||||||||
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.6 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 109180 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||
Atomic model building | PDB-ID: 6DO1 | ||||||||||||||||||||||||
Refinement | Cross valid method: NONE Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
Displacement parameters | Biso mean: 46.52 Å2 | ||||||||||||||||||||||||
Refine LS restraints |
|