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- EMDB-30505: Cryo-EM structure of the human growth hormone-releasing hormone r... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-30505 | |||||||||
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Title | Cryo-EM structure of the human growth hormone-releasing hormone receptor-Gs protein complex | |||||||||
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![]() | cognate receptor / Class B G-protein-coupled receptors / single particle / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() regulation of intracellular steroid hormone receptor signaling pathway / somatotropin secreting cell development / growth hormone-releasing hormone receptor binding / positive regulation of circadian sleep/wake cycle, REM sleep / growth hormone-releasing hormone activity / growth hormone-releasing hormone receptor activity / multicellular organismal reproductive process / growth hormone secretion / adenohypophysis development / positive regulation of growth hormone secretion ...regulation of intracellular steroid hormone receptor signaling pathway / somatotropin secreting cell development / growth hormone-releasing hormone receptor binding / positive regulation of circadian sleep/wake cycle, REM sleep / growth hormone-releasing hormone activity / growth hormone-releasing hormone receptor activity / multicellular organismal reproductive process / growth hormone secretion / adenohypophysis development / positive regulation of growth hormone secretion / regulation of protein metabolic process / neuropeptide hormone activity / positive regulation of multicellular organism growth / 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 / nuclear outer membrane / 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 / hormone metabolic process / Vasopressin regulates renal water homeostasis via Aquaporins / G protein-coupled peptide receptor activity / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / nuclear inner membrane / G alpha (q) signalling events / positive regulation of insulin-like growth factor receptor signaling pathway / 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 / response to food / photoreceptor outer segment membrane / G alpha (q) signalling events / peptide hormone receptor binding / 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 / growth factor binding / alkylglycerophosphoethanolamine phosphodiesterase activity / peptide hormone binding / PKA activation in glucagon signalling / hair follicle placode formation / photoreceptor outer segment / developmental growth / D1 dopamine receptor binding / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / response to glucocorticoid / Hedgehog 'off' state / cell maturation / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / photoreceptor inner segment / lactation / cardiac muscle cell apoptotic process / regulation of insulin secretion / cellular response to glucagon stimulus / adenylate cyclase activator activity / secretory granule / trans-Golgi network membrane / determination of adult lifespan / establishment of localization in cell / response to insulin / negative regulation of inflammatory response to antigenic stimulus / G protein-coupled receptor activity / terminal bouton / bone development / multicellular organism growth Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.6 Å | |||||||||
![]() | Zhou F / Zhang H | |||||||||
![]() | ![]() Title: Structural basis for activation of the growth hormone-releasing hormone receptor. Authors: Fulai Zhou / Huibing Zhang / Zhaotong Cong / Li-Hua Zhao / Qingtong Zhou / Chunyou Mao / Xi Cheng / Dan-Dan Shen / Xiaoqing Cai / Cheng Ma / Yuzhe Wang / Antao Dai / Yan Zhou / Wen Sun / ...Authors: Fulai Zhou / Huibing Zhang / Zhaotong Cong / Li-Hua Zhao / Qingtong Zhou / Chunyou Mao / Xi Cheng / Dan-Dan Shen / Xiaoqing Cai / Cheng Ma / Yuzhe Wang / Antao Dai / Yan Zhou / Wen Sun / Fenghui Zhao / Suwen Zhao / Hualiang Jiang / Yi Jiang / Dehua Yang / H Eric Xu / Yan Zhang / Ming-Wei Wang / ![]() Abstract: Growth hormone-releasing hormone (GHRH) regulates the secretion of growth hormone that virtually controls metabolism and growth of every tissue through its binding to the cognate receptor (GHRHR). ...Growth hormone-releasing hormone (GHRH) regulates the secretion of growth hormone that virtually controls metabolism and growth of every tissue through its binding to the cognate receptor (GHRHR). Malfunction in GHRHR signaling is associated with abnormal growth, making GHRHR an attractive therapeutic target against dwarfism (e.g., isolated growth hormone deficiency, IGHD), gigantism, lipodystrophy and certain cancers. Here, we report the cryo-electron microscopy (cryo-EM) structure of the human GHRHR bound to its endogenous ligand and the stimulatory G protein at 2.6 Å. This high-resolution structure reveals a characteristic hormone recognition pattern of GHRH by GHRHR, where the α-helical GHRH forms an extensive and continuous network of interactions involving all the extracellular loops (ECLs), all the transmembrane (TM) helices except TM4, and the extracellular domain (ECD) of GHRHR, especially the N-terminus of GHRH that engages a broad set of specific interactions with the receptor. Mutagenesis and molecular dynamics (MD) simulations uncover detailed mechanisms by which IGHD-causing mutations lead to the impairment of GHRHR function. Our findings provide insights into the molecular basis of peptide recognition and receptor activation, thereby facilitating the development of structure-based drug discovery and precision medicine. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 40 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 22 KB 22 KB | Display Display | ![]() |
Images | ![]() | 48.6 KB | ||
Filedesc metadata | ![]() | 7.3 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 542.2 KB | Display | ![]() |
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Full document | ![]() | 541.8 KB | Display | |
Data in XML | ![]() | 5.8 KB | Display | |
Data in CIF | ![]() | 6.7 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7cz5MC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.014 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
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Sample components
+Entire : Growth hormone-releasing hormone receptor - Gs protein complex
+Supramolecule #1: Growth hormone-releasing hormone receptor - Gs protein complex
+Supramolecule #2: hormone receptor, G(s) subunit alpha isoforms
+Supramolecule #3: hormone
+Supramolecule #4: G(s) subunit beta-1
+Supramolecule #5: G(s) subunit gamma-2
+Supramolecule #6: Nanobody35
+Macromolecule #1: Growth hormone-releasing hormone receptor,growth hormone-releasin...
+Macromolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #3: Somatoliberin
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #6: Nanobody35
+Macromolecule #7: PALMITIC ACID
+Macromolecule #8: CHOLESTEROL
+Macromolecule #9: water
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 QUANTUM (4k x 4k) / Detector mode: COUNTING / Average electron dose: 62.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |