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- PDB-7tyi: Calcitonin Receptor in complex with Gs and rat amylin peptide, CT... -
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Open data
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Basic information
Entry | Database: PDB / ID: 7tyi | ||||||||||||||||||||||||
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Title | Calcitonin Receptor in complex with Gs and rat amylin peptide, CT-like state | ||||||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / Amylin receptor / GPCR / calcitonin / CT-like | ||||||||||||||||||||||||
Function / homology | ![]() Calcitonin-like ligand receptors / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 / amylin receptor activity / calcitonin receptor activity / calcitonin gene-related peptide receptor activity / amylin receptor signaling pathway ...Calcitonin-like ligand receptors / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 / amylin receptor activity / calcitonin receptor activity / calcitonin gene-related peptide receptor activity / amylin receptor signaling pathway / positive regulation of adenylate cyclase activity / Calcitonin-like ligand receptors / positive regulation of cAMP-mediated signaling / negative regulation of ossification / negative regulation of bone resorption / eating behavior / negative regulation of osteoclast differentiation / positive regulation of protein kinase A signaling / PKA activation in glucagon signalling / response to amyloid-beta / hair follicle placode formation / mu-type opioid receptor binding / developmental growth / corticotropin-releasing hormone receptor 1 binding / intracellular transport / D1 dopamine receptor binding / Hedgehog 'off' state / positive regulation of calcium-mediated signaling / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / response to glucocorticoid / bone resorption / sensory perception of pain / regulation of mRNA stability / activation of adenylate cyclase activity / adenylate cyclase activator activity / ossification / osteoclast differentiation / acrosomal vesicle / trans-Golgi network membrane / secretory granule / ionotropic glutamate receptor binding / insulin-like growth factor receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / bone development / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / hormone activity / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / cilium / platelet aggregation / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / glucose metabolic process / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / positive regulation of cold-induced thermogenesis / amyloid-beta binding / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / G alpha (s) signalling events Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||||||||||||||
![]() | Cao, J. / Belousoff, M.J. / Johnson, R.M. / Wootten, D.L. / Sexton, P.M. | ||||||||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: A structural basis for amylin receptor phenotype. Authors: Jianjun Cao / Matthew J Belousoff / Yi-Lynn Liang / Rachel M Johnson / Tracy M Josephs / Madeleine M Fletcher / Arthur Christopoulos / Debbie L Hay / Radostin Danev / Denise Wootten / Patrick M Sexton / ![]() ![]() ![]() Abstract: Amylin receptors (AMYRs) are heterodimers of the calcitonin (CT) receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs), AMYR, AMYR, and AMYR. Selective AMYR agonists and dual ...Amylin receptors (AMYRs) are heterodimers of the calcitonin (CT) receptor (CTR) and one of three receptor activity-modifying proteins (RAMPs), AMYR, AMYR, and AMYR. Selective AMYR agonists and dual AMYR/CTR agonists are being developed as obesity treatments; however, the molecular basis for peptide binding and selectivity is unknown. We determined the structure and dynamics of active AMYRs with amylin, AMYR with salmon CT (sCT), AMYR with sCT or human CT (hCT), and CTR with amylin, sCT, or hCT. The conformation of amylin-bound complexes was similar for all AMYRs, constrained by the RAMP, and an ordered midpeptide motif that we call the bypass motif. The CT-bound AMYR complexes were distinct, overlapping the CT-bound CTR complexes. Our findings indicate that activation of AMYRs by CT-based peptides is distinct from their activation by amylin-based peptides. This has important implications for the development of AMYR therapeutics. | ||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 223.3 KB | Display | ![]() |
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PDB format | ![]() | 179.6 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.2 MB | Display | ![]() |
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Full document | ![]() | 1.3 MB | Display | |
Data in XML | ![]() | 47.8 KB | Display | |
Data in CIF | ![]() | 70.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 26180MC ![]() 7tyfC ![]() 7tyhC ![]() 7tylC ![]() 7tynC ![]() 7tyoC ![]() 7tywC ![]() 7tyxC ![]() 7tyyC ![]() 7tzfC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#1: Protein | Mass: 45685.406 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#2: Protein | Mass: 38534.062 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#3: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Antibody / Protein/peptide / Protein / Non-polymers / Sugars , 5 types, 15 molecules NPR![](data/chem/img/PLM.gif)
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#4: Antibody | Mass: 15140.742 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() | ||
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#5: Protein/peptide | Mass: 3924.426 Da / Num. of mol.: 1 / Fragment: UNP residues 38-74 / Source method: obtained synthetically / Source: (synth.) ![]() ![]() | ||
#6: Protein | Mass: 58469.594 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() | ||
#7: Chemical | ChemComp-PLM / #8: Sugar | |
-Details
Has ligand of interest | Y |
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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 |
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Sample preparation
Component | Name: Calcitonin Receptor in complex with Gs and rat amylin peptide, CT-like state Type: COMPLEX / Entity ID: #1-#6 / Source: MULTIPLE SOURCES |
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Molecular weight | Experimental value: NO |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 13 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy imaging
Microscopy | Model: TFS GLACIOS |
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Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.17_3644: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.3 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 140000 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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