+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-31824 | ||||||||||||||||||
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Title | Cryo-EM structure of the SV1-Gs complex. | ||||||||||||||||||
Map data | |||||||||||||||||||
Sample |
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Function / homology | Function and homology information growth hormone-releasing hormone receptor activity / 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 ...growth hormone-releasing hormone receptor activity / 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) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / 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 / photoreceptor outer segment / cardiac muscle cell apoptotic process / photoreceptor inner segment / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / sensory perception of taste / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / retina development in camera-type eye / GTPase binding / cell body / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / cellular response to hypoxia / cell population proliferation / membrane => GO:0016020 / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / GTPase activity / dendrite / protein-containing complex binding / membrane / plasma membrane / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) / Bos taurus (cattle) / synthetic construct (others) / Rattus norvegicus (Norway rat) | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | ||||||||||||||||||
Authors | Cong ZT / Zhou FL / Zhang C / Zou XY / Zhang HB / Wang YZ / Zhou QT / Cai XQ / Liu QF / Li J ...Cong ZT / Zhou FL / Zhang C / Zou XY / Zhang HB / Wang YZ / Zhou QT / Cai XQ / Liu QF / Li J / Shao LJ / Mao CY / Wang X / Wu JH / Xia T / Zhao LH / Jiang HL / Zhang Y / Xu HE / Cheng X / Yang DH / Wang MW | ||||||||||||||||||
Funding support | China, 5 items
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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 |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_31824.map.gz | 37.4 MB | EMDB map data format | |
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Header (meta data) | emd-31824-v30.xml emd-31824.xml | 17.1 KB 17.1 KB | Display Display | EMDB header |
Images | emd_31824.png | 53.1 KB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-31824 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-31824 | HTTPS FTP |
-Related structure data
Related structure data | 7v9lMC 7v9mC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_31824.map.gz / Format: CCP4 / Size: 42.9 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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Voxel size | X=Y=Z: 1.045 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Sample components
-Entire : Cryo-EM structure of the human growth hormone releasing hormone r...
Entire | Name: Cryo-EM structure of the human growth hormone releasing hormone receptor splice variant 1 in complex with G protein |
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Components |
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-Supramolecule #1: Cryo-EM structure of the human growth hormone releasing hormone r...
Supramolecule | Name: Cryo-EM structure of the human growth hormone releasing hormone receptor splice variant 1 in complex with G protein type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
-Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Macromolecule | Name: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 41.765363 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RATHRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...String: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RATHRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTSGIFETK FQVDKVNFHM FDVGAQRDER RKWIQCFNDV TAIIFVVDSS DYRLQEALND FK SIWNNRW LRTISVILFL NKQDLLAEKV LAGKSKIEDY FPEFARYTTP EDATPEPGED PRVTRAKYFI RDEFLRISTA SGD GRHYCY PHFTCSVDTE NARRIFNDCR DIIQRMHLRQ YELL |
-Macromolecule #2: GHRH receptor splice variant 1,GHRH receptor splice variant 1,GHR...
Macromolecule | Name: GHRH receptor splice variant 1,GHRH receptor splice variant 1,GHRH receptor splice variant 1,SV1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 57.750316 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MVPGTPSPLL GRGKELWLES LACLPGAVKR DCTITGWSEP FPPYPVACPV PLELLAEEES YFSTVKIIYT VGHSISIVAL FVAITILVA LRRLHCPRNY VHTQLFTTFI LKAGAVFLKD AALFHSDDTD HCSFSTVLCK VSVAASHFAT MTNFSWLLAE A VYLNCLLA ...String: MVPGTPSPLL GRGKELWLES LACLPGAVKR DCTITGWSEP FPPYPVACPV PLELLAEEES YFSTVKIIYT VGHSISIVAL FVAITILVA LRRLHCPRNY VHTQLFTTFI LKAGAVFLKD AALFHSDDTD HCSFSTVLCK VSVAASHFAT MTNFSWLLAE A VYLNCLLA STSPSSRRAF WWLVLAGWGL PVLFTGTWVS CKLAFEDIAC WDLDDTSPYW WIIKGPIVLS VGVNFGLFLN II RILVRKL EPAQGSLHTQ SQYWRLSKST LFLIPLFGIH YIIFNFLPDN AGLGIRLPLE LGLGSFQGFI VAILYCFLNQ EVR TEISRK WHGHDPELLP AWRTRGSSGG GGSGGGGSSG VFTLEDFVGD WEQTAAYNLD QVLEQGGVSS LLQNLAVSVT PIQR IVRSG ENALKIDIHV IIPYEGLSAD QMAQIEEVFK VVYPVDDHHF KVILPYGTLV IDGVTPNMLN YFGRPYEGIA VFDGK KITV TGTLWNGNKI IDERLITPDG SMLFRVTINS GGSENLYF |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Bos taurus (cattle) |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #4: Nanobody 35
Macromolecule | Name: Nanobody 35 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 15.343019 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: MAQVQLQESG GGLVQPGGSL RLSCAASGFT FSNYKMNWVR QAPGKGLEWV SDISQSGASI SYTGSVKGRF TISRDNAKNT LYLQMNSLK PEDTAVYYCA RCPAPFTRDC FDVTSTTYAY RGQGTQVTVS SHHHHHHEPE A |
-Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 40.226992 KDa |
Recombinant expression | Organism: Spodoptera frugiperda (fall armyworm) |
Sequence | String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD ...String: MGSLLQSELD QLRQEAEQLK NQIRDARKAC ADATLSQITN NIDPVGRIQM RTRRTLRGHL AKIYAMHWGT DSRLLVSASQ DGKLIIWDS YTTNKVHAIP LRSSWVMTCA YAPSGNYVAC GGLDNICSIY NLKTREGNVR VSRELAGHTG YLSCCRFLDD N QIVTSSGD TTCALWDIET GQQTTTFTGH TGDVMSLSLA PDTRLFVSGA CDASAKLWDV REGMCRQTFT GHESDINAIC FF PNGNAFA TGSDDATCRL FDLRADQELM TYSHDNIICG ITSVSFSKSG RLLLAGYDDF NCNVWDALKA DRAGVLAGHD NRV SCLGVT DDGMAVATGS WDSFLKIWNG SSGGGGSGGG GSSGVSGWRL FKKIS |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
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Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: OTHER |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 80.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
-Image processing
Startup model | Type of model: PDB ENTRY PDB model - PDB ID: |
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Initial angle assignment | Type: OTHER |
Final angle assignment | Type: OTHER |
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.6 Å / Resolution method: DIFFRACTION PATTERN/LAYERLINES / Number images used: 377241 |