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- EMDB-26197: Human Amylin2 Receptor in complex with Gs and rat amylin peptide -
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Open data
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Basic information
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Title | Human Amylin2 Receptor in complex with Gs and rat amylin peptide | ||||||||||||||||||||||||
![]() | post-processed consensus map | ||||||||||||||||||||||||
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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 | single particle reconstruction / cryo EM / Resolution: 2.55 Å | ||||||||||||||||||||||||
![]() | Cao J / Belousoff MJ / Johnson RM / Wootten DL / Sexton PM | ||||||||||||||||||||||||
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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 85.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 34.1 KB 34.1 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10 KB | Display | ![]() |
Images | ![]() | 28.8 KB | ||
Masks | ![]() | 91.1 MB | ![]() | |
Others | ![]() ![]() ![]() ![]() ![]() ![]() ![]() | 84.7 MB 84.5 MB 44.1 MB 45.9 MB 84.3 MB 84.7 MB 84.7 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 887.9 KB | Display | ![]() |
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Full document | ![]() | 887.5 KB | Display | |
Data in XML | ![]() | 18 KB | Display | |
Data in CIF | ![]() | 23.2 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7tyxMC ![]() 7tyfC ![]() 7tyhC ![]() 7tyiC ![]() 7tylC ![]() 7tynC ![]() 7tyoC ![]() 7tywC ![]() 7tyyC ![]() 7tzfC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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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Annotation | post-processed consensus map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
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Projections & Slices |
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Density Histograms |
-Additional map: Focussed refinement on G-proteins, Post-processed map, resampled on...
File | emd_26197_additional_1.map | ||||||||||||
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Annotation | Focussed refinement on G-proteins, Post-processed map, resampled on consensus refinement map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Focussed refinement on receptor, Post-processed map, resampled on...
File | emd_26197_additional_2.map | ||||||||||||
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Annotation | Focussed refinement on receptor, Post-processed map, resampled on consensus refinement map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Focussed refinement on receptor, unfiltered map, resampled on...
File | emd_26197_additional_3.map | ||||||||||||
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Annotation | Focussed refinement on receptor, unfiltered map, resampled on consensus refinement map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: unfiltered consensus map
File | emd_26197_additional_4.map | ||||||||||||
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Annotation | unfiltered consensus map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Composite map where focussed refinements on receptor and...
File | emd_26197_additional_5.map | ||||||||||||
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Annotation | Composite map where focussed refinements on receptor and g-proteins were resampled on the consensus refinement | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 1
File | emd_26197_half_map_1.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map 1
File | emd_26197_half_map_2.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
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Density Histograms |
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Sample components
+Entire : Human Amylin2 Receptor in complex with Gs and rat amylin peptide
+Supramolecule #1: Human Amylin2 Receptor in complex with Gs and rat amylin peptide
+Macromolecule #1: Receptor activity-modifying protein 2
+Macromolecule #2: amylin peptide
+Macromolecule #3: Calcitonin receptor
+Macromolecule #4: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #6: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #7: nanobody 35
+Macromolecule #8: PALMITIC ACID
+Macromolecule #9: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #10: CHOLESTEROL HEMISUCCINATE
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 4 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 61.8 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.6 µm / Nominal defocus min: 0.6 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |