+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-32144 | |||||||||
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Title | PTH-bound human PTH1R in complex with Gs (class3) | |||||||||
Map data | ||||||||||
Sample |
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Function / homology | Function and homology information type 1 parathyroid hormone receptor binding / parathyroid hormone receptor binding / negative regulation of bone mineralization involved in bone maturation / negative regulation of apoptotic process in bone marrow cell / positive regulation of osteoclast proliferation / response to parathyroid hormone / parathyroid hormone receptor activity / hormone-mediated apoptotic signaling pathway / positive regulation of cell proliferation in bone marrow / macromolecule biosynthetic process ...type 1 parathyroid hormone receptor binding / parathyroid hormone receptor binding / negative regulation of bone mineralization involved in bone maturation / negative regulation of apoptotic process in bone marrow cell / positive regulation of osteoclast proliferation / response to parathyroid hormone / parathyroid hormone receptor activity / hormone-mediated apoptotic signaling pathway / positive regulation of cell proliferation in bone marrow / macromolecule biosynthetic process / positive regulation of signal transduction / magnesium ion homeostasis / response to fibroblast growth factor / phosphate ion homeostasis / cAMP metabolic process / response to vitamin D / 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 / Ca2+ pathway / 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 / 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 / negative regulation of chondrocyte differentiation / 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 / osteoblast development / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / positive regulation of inositol phosphate biosynthetic process / photoreceptor outer segment membrane / peptide hormone receptor binding / 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 / Rho protein signal transduction / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / positive regulation of glycogen biosynthetic process / photoreceptor outer segment / chondrocyte differentiation / bone resorption / positive regulation of bone mineralization / response to cadmium ion / cell maturation / homeostasis of number of cells within a tissue / cardiac muscle cell apoptotic process / photoreceptor inner segment / skeletal system development / positive regulation of D-glucose import / adenylate cyclase-activating G protein-coupled receptor signaling pathway / response to lead ion / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / hormone activity / 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 / cell-cell signaling / GTPase binding / retina development in camera-type eye Similarity search - Function | |||||||||
Biological species | Homo sapiens (human) / Rattus norvegicus (Norway rat) / Bos taurus (cattle) / unidentified (others) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.2 Å | |||||||||
Authors | Kobayashi K / Kusakizako T / Miyauchi H / Tomita A / Shihoya W / Yamashita K / Nishizawa T / Kato HE / Nureki O | |||||||||
Funding support | Japan, 1 items
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Citation | Journal: Mol Cell / Year: 2022 Title: Endogenous ligand recognition and structural transition of a human PTH receptor. Authors: Kazuhiro Kobayashi / Kouki Kawakami / Tsukasa Kusakizako / Hirotake Miyauchi / Atsuhiro Tomita / Kan Kobayashi / Wataru Shihoya / Keitaro Yamashita / Tomohiro Nishizawa / Hideaki E Kato / ...Authors: Kazuhiro Kobayashi / Kouki Kawakami / Tsukasa Kusakizako / Hirotake Miyauchi / Atsuhiro Tomita / Kan Kobayashi / Wataru Shihoya / Keitaro Yamashita / Tomohiro Nishizawa / Hideaki E Kato / Asuka Inoue / Osamu Nureki / Abstract: Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. Intriguingly, ...Endogenous parathyroid hormone (PTH) and PTH-related peptide (PTHrP) bind to the parathyroid hormone receptor 1 (PTH1R) and activate the stimulatory G-protein (Gs) signaling pathway. Intriguingly, the two ligands have distinct signaling and physiological properties: PTH evokes prolonged Gs activation, whereas PTHrP evokes transient Gs activation with reduced bone-resorption effects. The distinct molecular actions are ascribed to the differences in ligand recognition and dissociation kinetics. Here, we report cryoelectron microscopic structures of six forms of the human PTH1R-Gs complex in the presence of PTH or PTHrP at resolutions of 2.8 -4.1 Å. A comparison of the PTH-bound and PTHrP-bound structures reveals distinct ligand-receptor interactions underlying the ligand affinity and selectivity. Furthermore, five distinct PTH-bound structures, combined with computational analyses, provide insights into the unique and complex process of ligand dissociation from the receptor and shed light on the distinct durations of signaling induced by PTH and PTHrP. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_32144.map.gz | 1.6 MB | EMDB map data format | |
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Header (meta data) | emd-32144-v30.xml emd-32144.xml | 25.1 KB 25.1 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_32144_fsc.xml | 7.5 KB | Display | FSC data file |
Images | emd_32144.png | 99.8 KB | ||
Masks | emd_32144_msk_1.map | 10 MB | Mask map | |
Others | emd_32144_additional_1.map.gz emd_32144_half_map_1.map.gz emd_32144_half_map_2.map.gz | 9.3 MB 9.3 MB 9.3 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-32144 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32144 | HTTPS FTP |
-Validation report
Summary document | emd_32144_validation.pdf.gz | 698.4 KB | Display | EMDB validaton report |
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Full document | emd_32144_full_validation.pdf.gz | 698 KB | Display | |
Data in XML | emd_32144_validation.xml.gz | 12.5 KB | Display | |
Data in CIF | emd_32144_validation.cif.gz | 16.2 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32144 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-32144 | HTTPS FTP |
-Related structure data
Related structure data | 7vvmMC 7vvjC 7vvkC 7vvlC 7vvnC 7vvoC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_32144.map.gz / Format: CCP4 / Size: 10 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.10667 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_32144_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: #1
File | emd_32144_additional_1.map | ||||||||||||
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Density Histograms |
-Half map: #2
File | emd_32144_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_32144_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
+Entire : endogenous ligand-bound the human PTH receptor in complex with Gs
+Supramolecule #1: endogenous ligand-bound the human PTH receptor in complex with Gs
+Supramolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Supramolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Supramolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Supramolecule #5: nanobody Nb35
+Supramolecule #6: Parathyroid hormone
+Supramolecule #7: Parathyroid hormone/parathyroid hormone-related peptide receptor
+Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: nanobody Nb35
+Macromolecule #5: Parathyroid hormone
+Macromolecule #6: Parathyroid hormone/parathyroid hormone-related peptide receptor
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 10 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 64.319 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: OTHER / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.6 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |