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- PDB-8f2a: Human Amylin3 Receptor in complex with Gs and Pramlintide analogu... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8f2a | |||||||||||||||||||||||||||
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Title | Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385 (Cluster 5 conformation) | |||||||||||||||||||||||||||
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![]() | SIGNALING PROTEIN/IMMUNE SYSTEM / GPCR / amylin receptor / receptor activity-modifying protein / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||||||||||||||
Function / homology | ![]() G protein-coupled receptor signaling pathway involved in heart process / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / 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 ...G protein-coupled receptor signaling pathway involved in heart process / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / 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 / negative regulation of ossification / positive regulation of receptor recycling / 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 / coreceptor activity / positive regulation of calcium-mediated signaling / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / response to glucocorticoid / cellular response to hormone stimulus / regulation of mRNA stability / activation of adenylate cyclase activity / adenylate cyclase activator activity / ossification / osteoclast differentiation / acrosomal vesicle / trans-Golgi network membrane / cellular response to estradiol stimulus / protein localization to plasma membrane / positive regulation of 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 / 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 / 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 / calcium ion transport / 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 / protein transport / 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 Similarity search - Function | |||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() | |||||||||||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.2 Å | |||||||||||||||||||||||||||
![]() | Cao, J. / Sexton, P.M. / Wootten, D.L. / Radostin, D. | |||||||||||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: Structural insight into selectivity of amylin and calcitonin receptor agonists. Authors: Jianjun Cao / Matthew J Belousoff / Elliot Gerrard / Radostin Danev / Madeleine M Fletcher / Emma Dal Maso / Herman Schreuder / Katrin Lorenz / Andreas Evers / Garima Tiwari / Melissa ...Authors: Jianjun Cao / Matthew J Belousoff / Elliot Gerrard / Radostin Danev / Madeleine M Fletcher / Emma Dal Maso / Herman Schreuder / Katrin Lorenz / Andreas Evers / Garima Tiwari / Melissa Besenius / Ziyu Li / Rachel M Johnson / Denise Wootten / Patrick M Sexton / ![]() ![]() ![]() ![]() ![]() Abstract: Amylin receptors (AMYRs), heterodimers of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins, are promising obesity targets. A hallmark of AMYR activation by Amy is ...Amylin receptors (AMYRs), heterodimers of the calcitonin receptor (CTR) and one of three receptor activity-modifying proteins, are promising obesity targets. A hallmark of AMYR activation by Amy is the formation of a 'bypass' secondary structural motif (residues S19-P25). This study explored potential tuning of peptide selectivity through modification to residues 19-22, resulting in a selective AMYR agonist, San385, as well as nonselective dual amylin and calcitonin receptor agonists (DACRAs), with San45 being an exemplar. We determined the structure and dynamics of San385-bound AMYR, and San45 bound to AMYR or CTR. San45, via its conjugated lipid at position 21, was anchored at the edge of the receptor bundle, enabling a stable, alternative binding mode when bound to the CTR, in addition to the bypass mode of binding to AMYR. Targeted lipid modification may provide a single intervention strategy for design of long-acting, nonselective, Amy-based DACRAs with potential anti-obesity effects. | |||||||||||||||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 270.9 KB | Display | ![]() |
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PDB format | ![]() | 207.9 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 | ![]() | 48.9 KB | Display | |
Data in CIF | ![]() | 73.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 28810MC ![]() 8f0jC ![]() 8f0kC ![]() 8f2bC C: citing same article ( M: map data used to model this data |
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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
-Protein , 2 types, 2 molecules ER
#1: Protein | Mass: 16896.650 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 Mutation: S54N, G226A, E268A, A366S, N271K, K274D, R280K, T284D, I285T 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, 6 molecules PN![](data/chem/img/NAG.gif)
![](data/chem/img/NAG.gif)
#2: Protein/peptide | Mass: 3995.524 Da / Num. of mol.: 1 / 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.) ![]() ![]() ![]() ![]() |
#8: Sugar | ChemComp-NAG / |
-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 amylin 3 receptor in complex with Gs protein and San385 peptide in another conformation (cluster 5) Type: COMPLEX / Entity ID: #1-#7 / Source: MULTIPLE SOURCES |
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Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
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: 1500 nm / Nominal defocus min: 500 nm |
Image recording | Electron dose: 70.1 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.20_4459: / Classification: refinement | ||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
3D reconstruction | Resolution: 2.2 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 118000 / Symmetry type: POINT | ||||||||||||
Atomic model building | B value: 35 / Protocol: AB INITIO MODEL / Space: REAL |