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- PDB-6oij: Muscarinic acetylcholine receptor 1-G11 protein complex -

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Basic information

Entry
Database: PDB / ID: 6oij
TitleMuscarinic acetylcholine receptor 1-G11 protein complex
Components
  • (Guanine nucleotide-binding protein ...) x 3
  • Antibody fragment
  • Muscarinic acetylcholine receptor M1
KeywordsSIGNALING PROTEIN / G-protein coupled receptor-G-protein complex / neurotransmitter receptor
Function / homology
Function and homology information


regulation of melanocyte differentiation / guanyl nucleotide binding / saliva secretion / regulation of glial cell proliferation / positive regulation of monoatomic ion transport / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / Muscarinic acetylcholine receptors / endothelin receptor signaling pathway / ion channel modulating, G protein-coupled receptor signaling pathway ...regulation of melanocyte differentiation / guanyl nucleotide binding / saliva secretion / regulation of glial cell proliferation / positive regulation of monoatomic ion transport / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / Muscarinic acetylcholine receptors / endothelin receptor signaling pathway / ion channel modulating, G protein-coupled receptor signaling pathway / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / developmental pigmentation / G protein-coupled acetylcholine receptor activity / neuromuscular synaptic transmission / cellular response to pH / cholinergic synapse / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / cranial skeletal system development / entrainment of circadian clock / phototransduction, visible light / positive regulation of intracellular protein transport / phosphatidylinositol phospholipase C activity / G protein-coupled serotonin receptor activity / protein kinase C-activating G protein-coupled receptor signaling pathway / regulation of locomotion / action potential / postsynaptic modulation of chemical synaptic transmission / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / ligand-gated ion channel signaling pathway / photoreceptor outer segment / regulation of postsynaptic membrane potential / enzyme regulator activity / axon terminus / G protein activity / skeletal system development / G protein-coupled receptor binding / postsynaptic density membrane / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Schaffer collateral - CA1 synapse / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / 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 / ADP signalling through P2Y purinoceptor 12 / positive regulation of insulin secretion / G beta:gamma signalling through BTK / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / cognition / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / regulation of blood pressure / 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 / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / G alpha (12/13) signalling events / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / presynaptic membrane / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / nervous system development / heart development / G alpha (i) signalling events / fibroblast proliferation / chemical synaptic transmission / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / lysosomal membrane
Similarity search - Function
Muscarinic acetylcholine receptor M1 / G-protein alpha subunit, group Q / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / Muscarinic acetylcholine receptor family / Rhopdopsin 7-helix transmembrane proteins / Rhodopsin 7-helix transmembrane proteins / YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H ...Muscarinic acetylcholine receptor M1 / G-protein alpha subunit, group Q / Transducin (heterotrimeric G protein), gamma chain / G Protein Gi Gamma 2 / Muscarinic acetylcholine receptor family / Rhopdopsin 7-helix transmembrane proteins / Rhodopsin 7-helix transmembrane proteins / YVTN repeat-like/Quinoprotein amine dehydrogenase / 7 Propeller / Methylamine Dehydrogenase; Chain H / G-alpha domain profile. / Guanine nucleotide binding protein (G-protein), alpha subunit / G protein alpha subunit, helical insertion / G-protein alpha subunit / G protein alpha subunit / G-protein, gamma subunit / G-protein gamma subunit domain profile. / GGL domain / G-protein gamma-like domain superfamily / G-protein gamma-like domain / GGL domain / G protein gamma subunit-like motifs / 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) / Few Secondary Structures / Irregular / G-protein beta WD-40 repeat / WD40 repeat, conserved site / Trp-Asp (WD) repeats signature. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / Trp-Asp (WD) repeats profile. / Trp-Asp (WD) repeats circular profile. / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily / Immunoglobulins / Up-down Bundle / Immunoglobulin-like / Sandwich / P-loop containing nucleoside triphosphate hydrolase / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
Chem-IXO / CHOLESTEROL HEMISUCCINATE / Guanine nucleotide-binding protein G(i) subunit alpha-1 / Muscarinic acetylcholine receptor M1 / Guanine nucleotide-binding protein subunit alpha-11 / 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
Similarity search - Component
Biological speciesHomo sapiens (human)
Mus musculus (house mouse)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å
AuthorsMaeda, S. / Qianhui, Q. / Skiniotis, G. / Kobilka, B.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01GM083118 United States
CitationJournal: Science / Year: 2019
Title: Structures of the M1 and M2 muscarinic acetylcholine receptor/G-protein complexes.
Authors: Shoji Maeda / Qianhui Qu / Michael J Robertson / Georgios Skiniotis / Brian K Kobilka /
Abstract: Muscarinic acetylcholine receptors are G protein-coupled receptors that respond to acetylcholine and play important signaling roles in the nervous system. There are five muscarinic receptor subtypes ...Muscarinic acetylcholine receptors are G protein-coupled receptors that respond to acetylcholine and play important signaling roles in the nervous system. There are five muscarinic receptor subtypes (M1R to M5R), which, despite sharing a high degree of sequence identity in the transmembrane region, couple to different heterotrimeric GTP-binding proteins (G proteins) to transmit signals. M1R, M3R, and M5R couple to the G family, whereas M2R and M4R couple to the G family. Here, we present and compare the cryo-electron microscopy structures of M1R in complex with G and M2R in complex with G The M1R-G complex exhibits distinct features, including an extended transmembrane helix 5 and carboxyl-terminal receptor tail that interacts with G protein. Detailed analysis of these structures provides a framework for understanding the molecular determinants of G-protein coupling selectivity.
History
DepositionApr 9, 2019Deposition site: RCSB / Processing site: RCSB
Revision 1.0May 8, 2019Provider: repository / Type: Initial release
Revision 1.1May 22, 2019Group: Data collection / Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2May 29, 2019Group: Data collection / Database references / Category: citation_author / Item: _citation_author.identifier_ORCID
Revision 1.3Jan 8, 2020Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization

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Structure visualization

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Assembly

Deposited unit
A: Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein subunit alpha-11
R: Muscarinic acetylcholine receptor M1
H: Antibody fragment
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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)156,6138
Polymers155,4425
Non-polymers1,1713
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551
Buried area11660 Å2
ΔGint-75 kcal/mol
Surface area50050 Å2

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Components

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Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG

#1: Protein Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein subunit alpha-11 / G-protein subunit alpha-11 / Guanine nucleotide-binding protein G(y) subunit alpha


Mass: 41271.086 Da / Num. of mol.: 1
Mutation: chimeric protein between G-alpha1i(1-29) and G-alpha11(30-)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNAI1, GNA11, GA11 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: A0A3B3ITX3, UniProt: P29992
#4: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 37728.152 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: GNB1 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P62873
#5: 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.) Homo sapiens (human) / Gene: GNG2 / Production host: Trichoplusia ni (cabbage looper) / References: UniProt: P59768

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Protein / Antibody , 2 types, 2 molecules RH

#2: Protein Muscarinic acetylcholine receptor M1 /


Mass: 41241.262 Da / Num. of mol.: 1 / Mutation: N11Q, N21Q
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: CHRM1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P11229
#3: Antibody Antibody fragment /


Mass: 27340.482 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Mus musculus (house mouse) / Production host: Trichoplusia ni (cabbage looper)

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Non-polymers , 2 types, 3 molecules

#6: Chemical ChemComp-IXO / 4-(4,5-dihydro-1,2-oxazol-3-yloxy)-N,N,N-trimethylbut-2-yn-1-aminium / Iperoxo


Mass: 197.254 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H17N2O2
#7: Chemical ChemComp-Y01 / CHOLESTEROL HEMISUCCINATE


Mass: 486.726 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C31H50O4

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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

Component
IDNameTypeEntity IDParent-IDSource
1muscarinic acetylcholine receptor 1 in complex with heterotrimeric G11 proteinCOMPLEX#1-#50RECOMBINANT
2Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein subunit alpha-11, Antibody fragment, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2COMPLEX#1, #3-#51RECOMBINANT
3Muscarinic acetylcholine receptor M1COMPLEX#21RECOMBINANT
Molecular weightValue: 0.15 MDa / Experimental value: NO
Source (natural)
IDEntity assembly-IDOrganismNcbi tax-ID
12Homo sapiens (human)9606
23Homo sapiens (human)9606
Source (recombinant)
IDEntity assembly-IDOrganismNcbi tax-ID
23Spodoptera frugiperda (fall armyworm)7108
12Trichoplusia ni (cabbage looper)7111
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportDetails: unspecified
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy
Image recordingElectron dose: 7 e/Å2 / Detector mode: COUNTING / Film or detector model: GATAN K2 SUMMIT (4k x 4k)

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Processing

EM softwareName: RELION / Version: 2.1 / Category: image acquisition
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 277988 / Symmetry type: POINT

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