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- EMDB-26196: Human Amylin1 Receptor in complex with Gs and salmon calcitonin p... -
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Open data
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Basic information
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Title | Human Amylin1 Receptor in complex with Gs and salmon calcitonin peptide | ||||||||||||||||||||||||
![]() | post-processed consensus map | ||||||||||||||||||||||||
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Function / homology | ![]() calcitonin receptor binding / calcitonin gene-related peptide binding / CGRP receptor complex / calcitonin gene-related peptide receptor signaling pathway / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / positive regulation of protein glycosylation / cross-receptor inhibition within G protein-coupled receptor heterodimer / amylin receptor complex 3 ...calcitonin receptor binding / calcitonin gene-related peptide binding / CGRP receptor complex / calcitonin gene-related peptide receptor signaling pathway / calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / positive regulation of protein glycosylation / 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 / regulation of G protein-coupled receptor signaling pathway / negative regulation of ossification / 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 / regulation of cytosolic calcium ion concentration / activation of adenylate cyclase activity / adenylate cyclase activator activity / ossification / osteoclast differentiation / acrosomal vesicle / trans-Golgi network membrane / 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 / 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 Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.0 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 | ![]() | 96.3 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 34.6 KB 34.6 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.7 KB | Display | ![]() |
Images | ![]() | 34.2 KB | ||
Others | ![]() ![]() ![]() ![]() ![]() ![]() ![]() | 81.2 MB 90.4 MB 92.9 MB 92.4 MB 94.9 MB 81.3 MB 81.3 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 797.8 KB | Display | ![]() |
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Full document | ![]() | 797.4 KB | Display | |
Data in XML | ![]() | 17.7 KB | Display | |
Data in CIF | ![]() | 23.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7tywMC ![]() 7tyfC ![]() 7tyhC ![]() 7tyiC ![]() 7tylC ![]() 7tynC ![]() 7tyoC ![]() 7tyxC ![]() 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
File | ![]() | ||||||||||||||||||||
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Annotation | post-processed consensus map | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.856 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Additional map: unfiltered consensus map
File | emd_26196_additional_1.map | ||||||||||||
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Annotation | unfiltered consensus map | ||||||||||||
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Density Histograms |
-Additional map: unfiltered map of local refinement that focused on...
File | emd_26196_additional_2.map | ||||||||||||
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Annotation | unfiltered map of local refinement that focused on extracellular domain and the map was resampled to the consensus map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: post-processed map of local refinement that focused on...
File | emd_26196_additional_3.map | ||||||||||||
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Annotation | post-processed map of local refinement that focused on extracellular domain and the map was resampled to the consensus map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: unfiltered map of local refinement that focused on...
File | emd_26196_additional_4.map | ||||||||||||
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Annotation | unfiltered map of local refinement that focused on receptor region and the map was resampled to the consensus map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: post-processed map of local refinement that focused on...
File | emd_26196_additional_5.map | ||||||||||||
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Annotation | post-processed map of local refinement that focused on receptor region and the map was resampled to the consensus map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map of the consensus map
File | emd_26196_half_map_1.map | ||||||||||||
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Annotation | half map of the consensus map | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map of the consensus map
File | emd_26196_half_map_2.map | ||||||||||||
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Annotation | half map of the consensus map | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
+Entire : Human Amylin 1 Receptor in complex with Gs and salmon calcitonin ...
+Supramolecule #1: Human Amylin 1 Receptor in complex with Gs and salmon calcitonin ...
+Macromolecule #1: Receptor activity-modifying protein 1
+Macromolecule #2: Calcitonin-1
+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
+Macromolecule #11: water
-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 GLACIOS |
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Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 200 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm |