[English] 日本語
Yorodumi- PDB-7v9m: Cryo-EM structure of the GHRH-bound human GHRHR splice variant 1 ... -
+Open data
-Basic information
Entry | Database: PDB / ID: 7v9m | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Cryo-EM structure of the GHRH-bound human GHRHR splice variant 1 complex | ||||||||||||||||||
Components |
| ||||||||||||||||||
Keywords | STRUCTURAL PROTEIN / class B GPCR / receptor bias / cancer / cell proliferation | ||||||||||||||||||
Function / homology | Function and homology information growth hormone-releasing hormone receptor binding / positive regulation of circadian sleep/wake cycle, REM sleep / growth hormone-releasing hormone activity / growth hormone secretion / adenohypophysis development / positive regulation of growth hormone secretion / neuropeptide hormone activity / positive regulation of multicellular organism growth / G-protein activation / Activation of the phototransduction cascade ...growth hormone-releasing hormone receptor binding / positive regulation of circadian sleep/wake cycle, REM sleep / growth hormone-releasing hormone activity / growth hormone secretion / adenohypophysis development / positive regulation of growth hormone secretion / neuropeptide hormone activity / positive regulation of multicellular organism growth / G-protein activation / Activation of the phototransduction cascade / : / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / Activation of G protein gated Potassium channels / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / alkylglycerophosphoethanolamine phosphodiesterase activity / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of insulin-like growth factor receptor signaling pathway / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / response to food / peptide hormone receptor binding / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / PKA activation in glucagon signalling / hair follicle placode formation / photoreceptor outer segment / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / positive regulation of cAMP-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / cardiac muscle cell apoptotic process / activation of adenylate cyclase activity / adenylate cyclase activator activity / photoreceptor inner segment / trans-Golgi network membrane / multicellular organism growth / G-protein beta/gamma-subunit complex binding / bone development / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / terminal bouton / cognition / platelet aggregation / Glucagon-type ligand receptors / positive regulation of GTPase activity / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / sensory perception of smell / signaling receptor complex adaptor activity / cell-cell signaling / retina development in camera-type eye Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) Rattus norvegicus (Norway rat) synthetic construct (others) Bos taurus (cattle) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.29 Å | ||||||||||||||||||
Authors | Cong, Z.T. / Zhou, F.L. / Zhang, C. / Zou, X.Y. / Zhang, H.B. / Wang, Y.Z. / Zhou, Q.T. / Cai, X.Q. / Liu, Q.F. / Li, J. ...Cong, Z.T. / Zhou, F.L. / Zhang, C. / Zou, X.Y. / Zhang, H.B. / Wang, Y.Z. / Zhou, Q.T. / Cai, X.Q. / Liu, Q.F. / Li, J. / Shao, L.J. / Mao, C.Y. / Wang, X. / Wu, J.H. / Xia, T. / Zhao, L.H. / Jiang, H.L. / Zhang, Y. / Xu, H.E. / Chen, X. / Yang, D.H. / Wang, M.W. | ||||||||||||||||||
Funding support | China, 5items
| ||||||||||||||||||
Citation | Journal: Proc Natl Acad Sci U S A / Year: 2021 Title: Constitutive signal bias mediated by the human GHRHR splice variant 1. Authors: Zhaotong Cong / Fulai Zhou / Chao Zhang / Xinyu Zou / Huibing Zhang / Yuzhe Wang / Qingtong Zhou / Xiaoqing Cai / Qiaofeng Liu / Jie Li / Lijun Shao / Chunyou Mao / Xi Wang / Jihong Wu / ...Authors: Zhaotong Cong / Fulai Zhou / Chao Zhang / Xinyu Zou / Huibing Zhang / Yuzhe Wang / Qingtong Zhou / Xiaoqing Cai / Qiaofeng Liu / Jie Li / Lijun Shao / Chunyou Mao / Xi Wang / Jihong Wu / Tian Xia / Li-Hua Zhao / Hualiang Jiang / Yan Zhang / H Eric Xu / Xi Cheng / Dehua Yang / Ming-Wei Wang / Abstract: Alternative splicing of G protein-coupled receptors has been observed, but their functions are largely unknown. Here, we report that a splice variant (SV1) of the human growth hormone-releasing ...Alternative splicing of G protein-coupled receptors has been observed, but their functions are largely unknown. Here, we report that a splice variant (SV1) of the human growth hormone-releasing hormone receptor (GHRHR) is capable of transducing biased signal. Differing only at the receptor N terminus, GHRHR predominantly activates G while SV1 selectively couples to β-arrestins. Based on the cryogenic electron microscopy structures of SV1 in the state or GHRH-bound state in complex with the G protein, molecular dynamics simulations reveal that the N termini of GHRHR and SV1 differentiate the downstream signaling pathways, G versus β-arrestins. As suggested by mutagenesis and functional studies, it appears that GHRH-elicited signal bias toward β-arrestin recruitment is constitutively mediated by SV1. The level of SV1 expression in prostate cancer cells is also positively correlated with ERK1/2 phosphorylation but negatively correlated with cAMP response. Our findings imply that constitutive signal bias may be a mechanism that ensures cancer cell proliferation. | ||||||||||||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7v9m.cif.gz | 197.3 KB | Display | PDBx/mmCIF format |
---|---|---|---|---|
PDB format | pdb7v9m.ent.gz | 154.8 KB | Display | PDB format |
PDBx/mmJSON format | 7v9m.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/v9/7v9m ftp://data.pdbj.org/pub/pdb/validation_reports/v9/7v9m | HTTPS FTP |
---|
-Related structure data
Related structure data | 31825MC 7v9lC M: map data used to model this data C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
-Assembly
Deposited unit |
|
---|---|
1 |
|
-Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABY
#1: Protein | Mass: 45683.434 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: GNAS, GNAS1, GSP / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63092 |
---|---|
#2: Protein | Mass: 40226.992 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Rattus norvegicus (Norway rat) / Gene: Gnb1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P54311 |
#6: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63212 |
-Antibody / Protein/peptide / Protein , 3 types, 3 molecules NPR
#3: Antibody | Mass: 15343.019 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) |
---|---|
#4: Protein/peptide | Mass: 5048.702 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: P01286 |
#5: Protein | Mass: 57878.441 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) |
-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Cryo-EM structure of the human growth hormone releasing hormone receptor splice variant 1 in complex with GHRH and G protein Type: COMPLEX / Entity ID: all / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera frugiperda (fall armyworm) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: OTHER / Accelerating voltage: 300 kV / Illumination mode: OTHER |
Electron lens | Mode: BRIGHT FIELDBright-field microscopy |
Image recording | Electron dose: 80 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.18.2_3874: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.29 Å / Resolution method: DIFFRACTION PATTERN/LAYERLINES / Num. of particles: 277500 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|