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- PDB-9lwp: Cryo-EM structure of the unliganded human BRS3-Gq complex -

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Entry
Database: PDB / ID: 9lwp
TitleCryo-EM structure of the unliganded human BRS3-Gq complex
Components
  • Bombesin receptor subtype-3,Oplophorus-luciferin 2-monooxygenase catalytic subunit
  • 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-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
KeywordsMEMBRANE PROTEIN / Unliganded
Function / homology
Function and homology information


bombesin receptor activity / Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway / neuropeptide receptor activity / adult feeding behavior / negative regulation of calcium ion-dependent exocytosis / G protein-coupled adenosine receptor signaling pathway / negative regulation of adenylate cyclase activity / positive regulation of urine volume ...bombesin receptor activity / Oplophorus-luciferin 2-monooxygenase / Oplophorus-luciferin 2-monooxygenase activity / negative regulation of adenylate cyclase-activating adrenergic receptor signaling pathway / neuropeptide receptor activity / adult feeding behavior / negative regulation of calcium ion-dependent exocytosis / G protein-coupled adenosine receptor signaling pathway / negative regulation of adenylate cyclase activity / positive regulation of urine volume / positive regulation of neural precursor cell proliferation / negative regulation of synaptic transmission / 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 / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / 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 / G alpha (i) signalling events / 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 / Thrombin signalling through proteinase activated receptors (PARs) / 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 / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / photoreceptor outer segment membrane / G alpha (q) signalling events / gamma-aminobutyric acid signaling pathway / G alpha (i) signalling events / spectrin binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / Vasopressin regulates renal water homeostasis via Aquaporins / neuronal dense core vesicle / alkylglycerophosphoethanolamine phosphodiesterase activity / regulation of calcium ion transport / negative regulation of apoptotic signaling pathway / PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / photoreceptor outer segment / D1 dopamine receptor binding / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / Hedgehog 'off' state / Adenylate cyclase inhibitory pathway / positive regulation of vascular associated smooth muscle cell proliferation / activation of adenylate cyclase activity / adenylate cyclase-activating adrenergic receptor signaling pathway / photoreceptor inner segment / cardiac muscle cell apoptotic process / response to nutrient / regulation of insulin secretion / cellular response to glucagon stimulus / adenylate cyclase activator activity / hippocampal mossy fiber to CA3 synapse / Peptide ligand-binding receptors / bioluminescence / positive regulation of superoxide anion generation / trans-Golgi network membrane / Regulation of insulin secretion / negative regulation of inflammatory response to antigenic stimulus / G protein-coupled receptor binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / bone development / regulation of blood pressure / G-protein beta/gamma-subunit complex binding / platelet aggregation / cognition / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway
Similarity search - Function
Bombesin receptor type 3 / Bombesin receptor-like / G protein beta WD-40 repeat protein / G-protein alpha subunit, group S / G-protein alpha subunit, group I / Calycin / Serpentine type 7TM GPCR chemoreceptor Srsx / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit ...Bombesin receptor type 3 / Bombesin receptor-like / G protein beta WD-40 repeat protein / G-protein alpha subunit, group S / G-protein alpha subunit, group I / Calycin / Serpentine type 7TM GPCR chemoreceptor Srsx / 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. / 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) subunit alpha-2 / Bombesin receptor subtype-3 / 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 / Oplophorus-luciferin 2-monooxygenase catalytic subunit
Similarity search - Component
Biological speciesHomo sapiens (human)
Oplophorus gracilirostris (crustacean)
Rattus norvegicus (Norway rat)
Bos taurus (domestic cattle)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.93 Å
AuthorsLi, J. / Li, C. / Zhou, Q. / Han, W. / Fang, M. / Xu, Y. / Mai, Y. / Cui, J. / Xu, H. / Zhang, Y. / Wang, M.
Funding support China, 17items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)82273961 China
National Natural Science Foundation of China (NSFC)82073904 China
National Natural Science Foundation of China (NSFC)81872915 China
National Natural Science Foundation of China (NSFC)32171189 China
National Natural Science Foundation of China (NSFC)32130022 China
Other government82121005
Other government2022YFA1302900
Other government2022YFC2703105
Other government2021278
Other governmentCXTD2023010
Other government2019B090904008
Other government2021B0909050003
Other governmentXDB37030103
Other government2019SHZDZX02
Other governmentLG-GG-202204-01
Other government2021ZD0203400
Other governmentZDKJ2021028
CitationJournal: Acta Pharm Sin B / Year: 2025
Title: Divergent activation patterns of BRS3 revealed by two Chinese herb-derived agonists
Authors: Li, J. / Li, C. / Zhou, Q. / Han, W. / Fang, M. / Xu, Y. / Mai, Y. / Zhang, Y. / Cui, J. / Xu, H.E. / Zhang, Y. / Yin, W. / Wang, M.W.
History
DepositionFeb 16, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Jul 16, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
R: Bombesin receptor subtype-3,Oplophorus-luciferin 2-monooxygenase catalytic subunit
A: Guanine nucleotide-binding protein G(i) subunit alpha-2,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


Theoretical massNumber of molelcules
Total (without water)141,1884
Polymers141,1884
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein Bombesin receptor subtype-3,Oplophorus-luciferin 2-monooxygenase catalytic subunit / BRS-3 / 19kOLase


Mass: 67457.555 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human), (gene. exp.) Oplophorus gracilirostris (crustacean)
Gene: BRS3 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P32247, UniProt: Q9GV45, Oplophorus-luciferin 2-monooxygenase
#2: Protein Guanine nucleotide-binding protein G(i) subunit alpha-2,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short / Adenylate cyclase-inhibiting G alpha protein / Adenylate cyclase-stimulating G alpha protein


Mass: 28084.832 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI2, GNAI2B, GNAS, GNAS1, GSP / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P04899, UniProt: P63092, Hydrolases; Acting on acid anhydrides; Acting on GTP to facilitate cellular and subcellular movement
#3: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 37915.496 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
#4: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 / G gamma-I


Mass: 7729.947 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
Has protein modificationN

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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 human BRS3-Gq complex
Type: COMPLEX / Entity ID: all / Source: RECOMBINANT
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
21Homo sapiens (human)9606
31Rattus norvegicus (Norway rat)10116
41Bos taurus (domestic cattle)9913
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: 2500 nm / Nominal defocus min: 1500 nm
Image recordingElectron dose: 80 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM software
IDNameVersionCategory
1SerialEMparticle selection
2PHENIX1.21_5207model refinement
13cryoSPARC3D reconstruction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 2.93 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 693649 / Symmetry type: POINT
RefinementHighest resolution: 2.93 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.0026983
ELECTRON MICROSCOPYf_angle_d0.4739462
ELECTRON MICROSCOPYf_dihedral_angle_d3.65943
ELECTRON MICROSCOPYf_chiral_restr0.041101
ELECTRON MICROSCOPYf_plane_restr0.0041188

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