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Open data
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Basic information
Entry | Database: PDB / ID: 7tyx | ||||||||||||||||||||||||
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Title | Human Amylin2 Receptor in complex with Gs and rat amylin peptide | ||||||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / Amylin receptor / GPCR / RAMP2 | ||||||||||||||||||||||||
Function / homology | ![]() Calcitonin-like ligand receptors / vascular associated smooth muscle cell development / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / adrenomedullin binding / basement membrane assembly / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 / adrenomedullin receptor activity ...Calcitonin-like ligand receptors / vascular associated smooth muscle cell development / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / adrenomedullin binding / basement membrane assembly / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 / adrenomedullin receptor activity / adrenomedullin receptor complex / adrenomedullin receptor signaling pathway / 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 / positive regulation of vasculogenesis / bicellular tight junction assembly / regulation of G protein-coupled receptor signaling pathway / adherens junction assembly / negative regulation of vascular permeability / negative regulation of ossification / negative regulation of bone resorption / sprouting angiogenesis / 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 / cellular response to vascular endothelial growth factor stimulus / vasculogenesis / Hedgehog 'off' state / coreceptor activity / negative regulation of endothelial cell apoptotic process / positive regulation of calcium-mediated signaling / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / clathrin-coated pit / response to glucocorticoid / bone resorption / cellular response to hormone stimulus / 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 / protein localization to plasma membrane / intracellular protein transport / 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 / receptor internalization / 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 / regulation of blood pressure / 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 Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.55 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 | ![]() | 245.4 KB | Display | ![]() |
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PDB format | ![]() | 196.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 50.4 KB | Display | |
Data in CIF | ![]() | 74.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 26197MC ![]() 7tyfC ![]() 7tyhC ![]() 7tyiC ![]() 7tylC ![]() 7tynC ![]() 7tyoC ![]() 7tywC ![]() 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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1 |
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Components
-Protein , 2 types, 2 molecules ER
#1: Protein | Mass: 17839.375 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#3: Protein | Mass: 58469.594 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Guanine nucleotide-binding protein ... , 3 types, 3 molecules ABG
#4: Protein | Mass: 45683.434 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
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#5: Protein | Mass: 38534.062 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
#6: Protein | Mass: 7861.143 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() |
-Protein/peptide / Antibody / Sugars , 3 types, 5 molecules PN![](data/chem/img/NAG.gif)
![](data/chem/img/NAG.gif)
#2: Protein/peptide | Mass: 3924.426 Da / Num. of mol.: 1 / Fragment: UNP residues 38-74 / Source method: obtained synthetically / Source: (synth.) ![]() ![]() |
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#7: Antibody | Mass: 15140.742 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() |
#9: Sugar |
-Non-polymers , 2 types, 10 molecules ![](data/chem/img/PLM.gif)
![](data/chem/img/Y01.gif)
![](data/chem/img/Y01.gif)
#8: Chemical | ChemComp-PLM / #10: Chemical | |
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-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: Human Amylin2 Receptor in complex with Gs and rat amylin peptide Type: COMPLEX / Entity ID: #1-#7 / Source: MULTIPLE SOURCES |
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Molecular weight | Experimental value: NO |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 4 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
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1600 nm / Nominal defocus min: 600 nm |
Image recording | Electron dose: 61.8 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k 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: 2.55 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 321000 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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