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- PDB-7x1t: Structure of Thyrotropin-Releasing Hormone Receptor bound with Ta... -

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Basic information

Entry
Database: PDB / ID: 7x1t
TitleStructure of Thyrotropin-Releasing Hormone Receptor bound with Taltirelin.
Components
  • (Guanine nucleotide-binding protein ...) x 2
  • ScFv16
  • Taltirelin
  • Thyrotropin-releasing hormone receptor
  • mini-G alpha q protein
KeywordsMEMBRANE PROTEIN / Thyrotropin-Releasing Hormone Receptor / Cryo-EM / Protirelin / agonist
Function / homology
Function and homology information


thyrotropin-releasing hormone receptor activity / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Activation of the phototransduction cascade / 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 ...thyrotropin-releasing hormone receptor activity / Olfactory Signaling Pathway / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Activation of the phototransduction cascade / 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 / G alpha (12/13) signalling events / 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 / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / G alpha (s) signalling events / G alpha (q) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (i) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Peptide ligand-binding receptors / photoreceptor disc membrane / cellular response to catecholamine stimulus / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) signalling events / G protein-coupled receptor signaling pathway / GTPase activity / membrane / plasma membrane / cytoplasm
Similarity search - Function
Thyrotropin-releasing hormone receptor / Serpentine type 7TM GPCR chemoreceptor Srsx / 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 ...Thyrotropin-releasing hormone receptor / Serpentine type 7TM GPCR chemoreceptor Srsx / 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. / WD domain, G-beta repeat / WD40 repeats / WD40 repeat / WD40-repeat-containing domain superfamily / WD40/YVTN repeat-like-containing domain superfamily
Similarity search - Domain/homology
: / Thyrotropin-releasing hormone receptor / 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-2
Similarity search - Component
Biological speciesBos taurus (cattle)
Homo sapiens (human)
Rattus norvegicus (Norway rat)
synthetic construct (others)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.26 Å
AuthorsYang, F. / Zhang, H.H. / Meng, X.Y. / Li, Y.G. / Zhou, Y.X. / Ling, S.L. / Liu, L. / Shi, P. / Tian, C.L.
Funding support China, 1items
OrganizationGrant numberCountry
Other government China
CitationJournal: Cell Res / Year: 2022
Title: Structural insights into thyrotropin-releasing hormone receptor activation by an endogenous peptide agonist or its orally administered analogue.
Authors: Fan Yang / Huanhuan Zhang / Xianyu Meng / Yingge Li / Yingxin Zhou / Shenglong Ling / Demeng Sun / Pei Lv / Lei Liu / Pan Shi / Changlin Tian /
History
DepositionFeb 24, 2022Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Aug 31, 2022Provider: repository / Type: Initial release
Revision 1.1Sep 14, 2022Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.identifier_ORCID
Revision 1.2Oct 23, 2024Group: Data collection / Derived calculations / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / em_admin / pdbx_entry_details / pdbx_modification_feature / struct_conn
Item: _em_admin.last_update / _pdbx_entry_details.has_protein_modification / _struct_conn.pdbx_leaving_atom_flag

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
F: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
A: Thyrotropin-releasing hormone receptor
B: mini-G alpha q protein
C: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
D: ScFv16
E: Taltirelin


Theoretical massNumber of molelcules
Total (without water)145,5716
Polymers145,5716
Non-polymers00
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

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Guanine nucleotide-binding protein ... , 2 types, 2 molecules FC

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


Mass: 7845.078 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
#4: Protein Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 / Transducin beta chain 1


Mass: 37416.930 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Bos taurus (cattle) / Gene: GNB1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P62871

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Protein , 2 types, 2 molecules AB

#2: Protein Thyrotropin-releasing hormone receptor / TRH-R / Thyroliberin receptor


Mass: 45119.672 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TRHR / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P34981
#3: Protein mini-G alpha q protein


Mass: 28085.816 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)

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Antibody / Protein/peptide , 2 types, 2 molecules DE

#5: Antibody ScFv16


Mass: 26679.721 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Rattus norvegicus (Norway rat) / Production host: Spodoptera frugiperda (fall armyworm)
#6: Protein/peptide Taltirelin


Type: Peptide-like / Class: Inhibitor / Mass: 423.424 Da / Num. of mol.: 1 / Source method: obtained synthetically / Source: (synth.) synthetic construct (others) / References: BIRD: PRD_002370

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Details

Has ligand of interestY
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: The Thyrotropin-Releasing Hormone Receptor and Gq heterotrimer complex
Type: COMPLEX / Entity ID: all / Source: MULTIPLE SOURCES
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 / Humidity: 100 %

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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: SPOT SCAN
Electron lensMode: DIFFRACTION / Nominal defocus max: 2200 nm / Nominal defocus min: 1200 nm
Image recordingElectron dose: 55 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

Software
NameVersionClassificationNB
phenix.real_space_refine1.14_3260refinement
PHENIX1.14_3260refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
3D reconstructionResolution: 3.26 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 394270 / Symmetry type: POINT
RefinementStereochemistry target values: CDL v1.2
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00477632
ELECTRON MICROSCOPYf_angle_d0.901210458
ELECTRON MICROSCOPYf_chiral_restr0.05771287
ELECTRON MICROSCOPYf_plane_restr0.00731330
ELECTRON MICROSCOPYf_dihedral_angle_d7.00424417

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