[English] 日本語
Yorodumi- EMDB-26208: Human Amylin3 Receptor in complex with Gs and rat amylin peptide -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-26208 | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Human Amylin3 Receptor in complex with Gs and rat amylin peptide | ||||||||||||||||||||||||
Map data | post-processed consensus map | ||||||||||||||||||||||||
Sample |
| ||||||||||||||||||||||||
Function / homology | Function and homology information Calcitonin-like ligand receptors / 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 ...Calcitonin-like ligand receptors / 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 / negative regulation of bone resorption / eating behavior / positive regulation of receptor recycling / 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 / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / positive regulation of cAMP-mediated signaling / coreceptor activity / positive regulation of calcium-mediated signaling / adenylate cyclase-activating adrenergic receptor signaling pathway / response to glucocorticoid / bone resorption / sensory perception of pain / 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 / secretory granule / cellular response to estradiol stimulus / protein localization to plasma membrane / positive regulation of protein localization to plasma membrane / intracellular protein transport / Olfactory Signaling Pathway / G-protein beta/gamma-subunit complex binding / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / bone development / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / cilium / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / hormone activity / ADP signalling through P2Y purinoceptor 12 / receptor internalization / G beta:gamma signalling through BTK / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / platelet aggregation / cognition / Vasopressin regulates renal water homeostasis via Aquaporins / positive regulation of GTPase activity / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / adenylate cyclase-activating dopamine receptor signaling pathway / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / sensory perception of taste / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / Inactivation, recovery and regulation of the phototransduction cascade / glucose metabolic process / calcium ion transport / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / sensory perception of smell / Thrombin signalling through proteinase activated receptors (PARs) / protein transport Similarity search - Function | ||||||||||||||||||||||||
Biological species | Homo sapiens (human) / Rattus norvegicus (Norway rat) / Lama glama (llama) | ||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.4 Å | ||||||||||||||||||||||||
Authors | Cao J / Belousoff MJ / Johnson RM / Wootten DL / Sexton PM | ||||||||||||||||||||||||
Funding support | Australia, Japan, 7 items
| ||||||||||||||||||||||||
Citation | Journal: Science / Year: 2022 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 |
|
-Structure visualization
Supplemental images |
---|
-Downloads & links
-EMDB archive
Map data | emd_26208.map.gz | 166.5 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-26208-v30.xml emd-26208.xml | 33 KB 33 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_26208_fsc.xml | 12.8 KB | Display | FSC data file |
Images | emd_26208.png | 28.2 KB | ||
Masks | emd_26208_msk_1.map | 178 MB | Mask map | |
Others | emd_26208_additional_1.map.gz emd_26208_additional_2.map.gz emd_26208_additional_3.map.gz emd_26208_additional_4.map.gz emd_26208_half_map_1.map.gz emd_26208_half_map_2.map.gz | 166.5 MB 161.7 MB 159.3 MB 141.5 MB 141.8 MB 141.8 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-26208 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26208 | HTTPS FTP |
-Related structure data
Related structure data | 7tzfMC 7tyfC 7tyhC 7tyiC 7tylC 7tynC 7tyoC 7tywC 7tyxC 7tyyC M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_26208.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | post-processed consensus map | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.65 Å | ||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | emd_26208_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: the combined map that samples the consensus map...
File | emd_26208_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | the combined map that samples the consensus map and the local refined map. | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: post-processed map from local refinement that focused on...
File | emd_26208_additional_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | post-processed map from local refinement that focused on receptor region and the map was resampled to the consensus map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: unfiltered map from local refinement that focused on...
File | emd_26208_additional_3.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | unfiltered map from local refinement that focused on receptor region and the map was resampled to the consensus map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: unfiltered consensus map
File | emd_26208_additional_4.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | unfiltered consensus map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map of the consensus map
File | emd_26208_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map of the consensus map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map of the consensus map
File | emd_26208_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map of the consensus map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
+Entire : Human Amylin 3 Receptor in complex with Gs and rat amylin peptide
+Supramolecule #1: Human Amylin 3 Receptor in complex with Gs and rat amylin peptide
+Macromolecule #1: Receptor activity-modifying protein 3
+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: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #9: (2S)-2-{[(1R)-1-hydroxyhexadecyl]oxy}-3-{[(1R)-1-hydroxyoctadecyl...
+Macromolecule #10: PALMITIC ACID
+Macromolecule #11: CHOLESTEROL HEMISUCCINATE
+Macromolecule #12: water
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4 mg/mL |
---|---|
Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | TFS KRIOS |
---|---|
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.5 µm |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 52.8 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |