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Yorodumi- PDB-6nbh: Cryo-EM structure of parathyroid hormone receptor type 1 in compl... -
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-Basic information
Entry | Database: PDB / ID: 6nbh | ||||||||||||||||||
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Title | Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein | ||||||||||||||||||
Components |
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Keywords | SIGNALING PROTEIN / Parathyroid hormone receptor / GPCR / Class B GPCR / GPCR-G protein complex | ||||||||||||||||||
Function / homology | Function and homology information parathyroid hormone receptor activity / sensory perception of chemical stimulus / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / 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 ...parathyroid hormone receptor activity / sensory perception of chemical stimulus / mu-type opioid receptor binding / corticotropin-releasing hormone receptor 1 binding / 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 / G protein-coupled peptide receptor activity / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / 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 / Class B/2 (Secretin family receptors) / Thrombin signalling through proteinase activated receptors (PARs) / 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 / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / osteoblast development / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / beta-2 adrenergic receptor binding / G alpha (s) signalling events / G alpha (q) signalling events / positive regulation of inositol phosphate biosynthetic process / 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 / bone mineralization / peptide hormone binding / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / cell maturation / photoreceptor outer segment / D1 dopamine receptor binding / chondrocyte differentiation / bone resorption / adenylate cyclase-activating adrenergic receptor signaling pathway / cardiac muscle cell apoptotic process / insulin-like growth factor receptor binding / adenylate cyclase activator activity / ionotropic glutamate receptor binding / photoreceptor inner segment / skeletal system development / G-protein beta/gamma-subunit complex binding / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / intracellular calcium ion homeostasis / cellular response to catecholamine stimulus / sensory perception of taste / 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 / GTPase binding / retina development in camera-type eye / cellular response to hypoxia / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / basolateral plasma membrane / cell body / G alpha (s) signalling events / in utero embryonic development / receptor complex / cell population proliferation / cell surface receptor signaling pathway / apical plasma membrane / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / GTPase activity / positive regulation of cell population proliferation / dendrite Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) Bos taurus (cattle) Rattus norvegicus (Norway rat) synthetic construct (others) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.5 Å | ||||||||||||||||||
Authors | Zhao, L.-H. / Ma, S. / Sutkeviciute, I. / Shen, D.-D. / Zhou, X.E. / de Waal, P.P. / Li, C.-Y. / Kang, Y. / Clark, L.J. / Jean-Alphonse, F.G. ...Zhao, L.-H. / Ma, S. / Sutkeviciute, I. / Shen, D.-D. / Zhou, X.E. / de Waal, P.P. / Li, C.-Y. / Kang, Y. / Clark, L.J. / Jean-Alphonse, F.G. / White, A.D. / Xiao, K. / Yang, D. / Jiang, Y. / Watanabe, T. / Gardella, T.J. / Melcher, K. / Wang, M.-W. / Vilardaga, J.-P. / Xu, H.E. / Zhang, Y. | ||||||||||||||||||
Funding support | China, United States, 5items
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Citation | Journal: Science / Year: 2019 Title: Structure and dynamics of the active human parathyroid hormone receptor-1. Authors: Li-Hua Zhao / Shanshan Ma / Ieva Sutkeviciute / Dan-Dan Shen / X Edward Zhou / Parker W de Waal / Chen-Yao Li / Yanyong Kang / Lisa J Clark / Frederic G Jean-Alphonse / Alex D White / Dehua ...Authors: Li-Hua Zhao / Shanshan Ma / Ieva Sutkeviciute / Dan-Dan Shen / X Edward Zhou / Parker W de Waal / Chen-Yao Li / Yanyong Kang / Lisa J Clark / Frederic G Jean-Alphonse / Alex D White / Dehua Yang / Antao Dai / Xiaoqing Cai / Jian Chen / Cong Li / Yi Jiang / Tomoyuki Watanabe / Thomas J Gardella / Karsten Melcher / Ming-Wei Wang / Jean-Pierre Vilardaga / H Eric Xu / Yan Zhang / Abstract: The parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to calcium homeostasis and a therapeutic target for osteoporosis and hypoparathyroidism. Here we report the ...The parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to calcium homeostasis and a therapeutic target for osteoporosis and hypoparathyroidism. Here we report the cryo-electron microscopy structure of human PTH1R bound to a long-acting PTH analog and the stimulatory G protein. The bound peptide adopts an extended helix with its amino terminus inserted deeply into the receptor transmembrane domain (TMD), which leads to partial unwinding of the carboxyl terminus of transmembrane helix 6 and induces a sharp kink at the middle of this helix to allow the receptor to couple with G protein. In contrast to a single TMD structure state, the extracellular domain adopts multiple conformations. These results provide insights into the structural basis and dynamics of PTH binding and receptor activation. | ||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 6nbh.cif.gz | 251.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6nbh.ent.gz | 203.1 KB | Display | PDB format |
PDBx/mmJSON format | 6nbh.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6nbh_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 6nbh_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 6nbh_validation.xml.gz | 35.3 KB | Display | |
Data in CIF | 6nbh_validation.cif.gz | 53.4 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nb/6nbh ftp://data.pdbj.org/pub/pdb/validation_reports/nb/6nbh | HTTPS FTP |
-Related structure data
Related structure data | 0411MC 0410C 0412C 6nbfC 6nbiC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein , 2 types, 2 molecules RA
#1: Protein | Mass: 54755.004 Da / Num. of mol.: 1 / Mutation: G188A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: PTH1R, PTHR, PTHR1 / Production host: Spodoptera (butterflies/moths) / References: UniProt: Q03431 |
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#3: Protein | Mass: 43867.762 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Production host: Spodoptera (butterflies/moths) / References: UniProt: P04896*PLUS |
-Guanine nucleotide-binding protein ... , 2 types, 2 molecules BG
#4: Protein | 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 (butterflies/moths) / References: UniProt: P54311 |
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#5: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Bos taurus (cattle) / Gene: GNG2 / Production host: Spodoptera (butterflies/moths) / References: UniProt: P63212 |
-Protein/peptide / Antibody , 2 types, 2 molecules PN
#2: Protein/peptide | Mass: 4274.027 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Production host: synthetic construct (others) |
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#6: Antibody | Mass: 13711.284 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) synthetic construct (others) / Production host: Escherichia coli (E. coli) |
-Non-polymers , 2 types, 10 molecules
#7: Chemical | ChemComp-CLR / #8: Chemical | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Cryo-EM structure of parathyroid hormone receptor type 1 in complex with a long-acting parathyroid hormone analog and G protein Type: COMPLEX / Entity ID: #1-#6 / Source: RECOMBINANT |
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Source (natural) | Organism: Homo sapiens (human) |
Source (recombinant) | Organism: Spodoptera (butterflies/moths) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 BASE (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: (1.13_2998: ???) / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 134774 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Protocol: RIGID BODY FIT | ||||||||||||||||||||||||
Refinement | Resolution: 3.5→49.676 Å / SU ML: 0.44 / σ(F): 0 / Phase error: 52.94 / Stereochemistry target values: MLHL
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Solvent computation | Shrinkage radii: 0.8 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL | ||||||||||||||||||||||||
Refine LS restraints |
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