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- PDB-24tb: Cryo-EM structure of the ligand-free (Apo) GHRHR-Gs complex -

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Basic information

Entry
Database: PDB / ID: 24tb
TitleCryo-EM structure of the ligand-free (Apo) GHRHR-Gs complex
Components
  • Growth hormone-releasing hormone receptor
  • 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(s) subunit alpha isoforms short
KeywordsMEMBRANE PROTEIN / GPCR / Complex
Function / homology
Function and homology information


growth hormone-releasing hormone receptor activity / positive regulation of circadian sleep/wake cycle, non-REM sleep / positive regulation of growth hormone secretion / 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 ...growth hormone-releasing hormone receptor activity / positive regulation of circadian sleep/wake cycle, non-REM sleep / positive regulation of growth hormone secretion / 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / positive regulation of insulin-like growth factor receptor signaling pathway / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G protein-coupled peptide receptor activity / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / nuclear inner membrane / 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 / G alpha (12/13) signalling events / Glucagon-type ligand receptors / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Ca2+ pathway / G alpha (z) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / spectrin binding / growth factor binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (i) signalling events / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / alkylglycerophosphoethanolamine phosphodiesterase activity / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / peptide hormone binding / nuclear outer membrane / regulation of skeletal muscle contraction / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / intracellular transport / cAMP/PKA signal transduction / photoreceptor outer segment / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / Hedgehog 'off' state / activation of adenylate cyclase activity / adenylate cyclase-activating adrenergic receptor signaling pathway / cellular response to acidic pH / cardiac muscle cell apoptotic process / photoreceptor inner segment / cellular response to glucagon stimulus / secretory granule / intracellular glucose homeostasis / response to glucocorticoid / adenylate cyclase activator activity / positive regulation of insulin secretion involved in cellular response to glucose stimulus / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / cellular response to glucose stimulus / response to prostaglandin E / sarcolemma / response to insulin / bone development / response to estrogen / platelet aggregation / cognition / G protein-coupled receptor activity / nuclear matrix / G-protein beta/gamma-subunit complex binding / positive regulation of insulin secretion / sensory perception of smell / Glucagon signaling in metabolic regulation / Prostacyclin signalling through prostacyclin receptor
Similarity search - Function
GPCR, family 2, growth hormone-releasing hormone receptor / G-protein coupled receptors family 2 signature 1. / : / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. / Domain present in hormone receptors / Hormone receptor domain / GPCR family 2, extracellular hormone receptor domain superfamily / G-protein coupled receptors family 2 signature 2. / GPCR, family 2, secretin-like, conserved site ...GPCR, family 2, growth hormone-releasing hormone receptor / G-protein coupled receptors family 2 signature 1. / : / GPCR, family 2, extracellular hormone receptor domain / G-protein coupled receptors family 2 profile 1. / Domain present in hormone receptors / Hormone receptor domain / GPCR family 2, extracellular hormone receptor domain superfamily / G-protein coupled receptors family 2 signature 2. / GPCR, family 2, secretin-like, conserved site / GPCR, family 2, secretin-like / 7 transmembrane receptor (Secretin family) / GPCR, family 2-like / G-protein coupled receptors family 2 profile 2. / G-protein alpha subunit, group S / G protein alpha subunit, helical insertion / G protein alpha subunit / Guanine nucleotide binding protein (G-protein), alpha subunit / G-protein alpha subunit / G-alpha domain profile. / 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 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
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / Growth hormone-releasing hormone receptor
Similarity search - Component
Biological speciesHomo sapiens (human)
Rattus norvegicus (Norway rat)
Bos taurus (domestic cattle)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.04 Å
AuthorsWang, M.W. / Hang, K.N. / Qiu, Y. / Chen, X.Y. / Chen, Y.Y. / Cong, Z.T. / Zhou, Q.T.
Funding support China, 2items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32200576 China
National Natural Science Foundation of China (NSFC)82273961 China
CitationJournal: Protein Cell / Year: 2026
Title: Structural adaptation associated with signaling preference at the human GHRHR.
Authors: Ming-Wei Wang / Kaini Hang / Yue Qiu / Xianyue Chen / Yanyan Chen / Shengtian Huang / Zhaotong Cong / Qingtong Zhou /
History
DepositionMar 19, 2026Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jul 8, 2026Provider: repository / Type: Initial release
Revision 1.0Jul 8, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
Revision 1.0Jul 8, 2026Data content type: Half map / Part number: 1 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 8, 2026Data content type: Half map / Part number: 2 / Data content type: Half map / Provider: repository / Type: Initial release
Revision 1.0Jul 8, 2026Data content type: Image / Data content type: Image / Provider: repository / Type: Initial release
Revision 1.0Jul 8, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
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: Growth hormone-releasing hormone receptor


Theoretical massNumber of molelcules
Total (without water)158,9034
Polymers158,9034
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1

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Components

#1: Protein Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / Adenylate cyclase-stimulating G alpha 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 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 43706.750 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
#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.) Bos taurus (domestic cattle) / Gene: GNG2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P63212
#4: Protein Growth hormone-releasing hormone receptor / GHRH receptor / Growth hormone-releasing factor receptor / GRF receptor / GRFR


Mass: 61651.438 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GHRHR / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: Q02643
Has protein modificationY

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Experimental details

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Experiment

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

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Sample preparation

ComponentName: Cryo-EM structure of the ligand-free (Apo) GHRHR-Gs complex
Type: COMPLEX / Entity ID: all / 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

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: OTHER / Accelerating voltage: 300 kV / Illumination mode: OTHER
Electron lensMode: BRIGHT FIELD / Nominal defocus max: 2000 nm / Nominal defocus min: 1000 nm
Image recordingElectron dose: 80 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameVersionCategoryImage processing-ID
1cryoSPARCparticle selection1
2PHENIX1.20.1_4487model refinement
13cryoSPARC3D reconstruction1
14cryoSPARCparticle selection2
19cryoSPARC3D reconstruction2
Image processing
IDImage recording-ID
11
21
CTF correction
IDEM image processing-IDType
11PHASE FLIPPING AND AMPLITUDE CORRECTION
22PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstruction
IDResolution (Å)Resolution methodNum. of particlesImage processing-IDEntry-IDSymmetry type
13.04FSC 0.143 CUT-OFF185622124TBPOINT
23.04FSC 0.143 CUT-OFF185622124TBPOINT
33.04FSC 0.143 CUT-OFF185622124TBPOINT
43.04FSC 0.143 CUT-OFF185622124TBPOINT
53.04FSC 0.143 CUT-OFF185622124TBPOINT
63.04FSC 0.143 CUT-OFF185622124TBPOINT
73.04FSC 0.143 CUT-OFF185622124TBPOINT
83.03FSC 0.143 CUT-OFF185622124TBPOINT
93.04FSC 0.143 CUT-OFF185622124TBPOINT
103.04FSC 0.143 CUT-OFF185622124TBPOINT
113.04FSC 0.143 CUT-OFF185622124TBPOINT
123.04FSC 0.143 CUT-OFF185622124TBPOINT
133.04FSC 0.143 CUT-OFF185622124TBPOINT
143.04FSC 0.143 CUT-OFF185622124TBPOINT
153.04FSC 0.143 CUT-OFF185622124TBPOINT
163.03FSC 0.143 CUT-OFF185622124TBPOINT
173.04FSC 0.143 CUT-OFF185622224TBPOINT
183.04FSC 0.143 CUT-OFF185622224TBPOINT
193.04FSC 0.143 CUT-OFF185622224TBPOINT
203.04FSC 0.143 CUT-OFF185622224TBPOINT
213.04FSC 0.143 CUT-OFF185622224TBPOINT
223.04FSC 0.143 CUT-OFF185622224TBPOINT
233.04FSC 0.143 CUT-OFF185622224TBPOINT
243.03FSC 0.143 CUT-OFF185622224TBPOINT
253.04FSC 0.143 CUT-OFF185622224TBPOINT
263.04FSC 0.143 CUT-OFF185622224TBPOINT
273.04FSC 0.143 CUT-OFF185622224TBPOINT
283.04FSC 0.143 CUT-OFF185622224TBPOINT
293.04FSC 0.143 CUT-OFF185622224TBPOINT
303.04FSC 0.143 CUT-OFF185622224TBPOINT
313.04FSC 0.143 CUT-OFF185622224TBPOINT
323.03FSC 0.143 CUT-OFF185622224TBPOINT
RefinementHighest resolution: 3.04 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0027123
ELECTRON MICROSCOPYf_angle_d0.3519651
ELECTRON MICROSCOPYf_dihedral_angle_d3.239951
ELECTRON MICROSCOPYf_chiral_restr0.0371089
ELECTRON MICROSCOPYf_plane_restr0.0031226

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