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Yorodumi- EMDB-20901: CryoEM Structure of the active Adrenomedullin 2 receptor G protei... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-20901 | ||||||||||||||||||
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Title | CryoEM Structure of the active Adrenomedullin 2 receptor G protein complex with adrenomedullin peptide | ||||||||||||||||||
Map data | Adrenomedullin 2 receptor G protein complex with adrenomedullin peptide Post Processed MAP | ||||||||||||||||||
Sample |
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Function / homology | Function and homology information adrenomedullin receptor binding / G protein-coupled receptor signaling pathway involved in heart process / positive regulation of progesterone biosynthetic process / CGRP receptor complex / calcitonin gene-related peptide receptor signaling pathway / vascular associated smooth muscle cell development / adrenomedullin binding / cross-receptor inhibition within G protein-coupled receptor heterodimer / cellular response to sucrose stimulus / amylin receptor complex 3 ...adrenomedullin receptor binding / G protein-coupled receptor signaling pathway involved in heart process / positive regulation of progesterone biosynthetic process / CGRP receptor complex / calcitonin gene-related peptide receptor signaling pathway / vascular associated smooth muscle cell development / adrenomedullin binding / cross-receptor inhibition within G protein-coupled receptor heterodimer / cellular response to sucrose stimulus / amylin receptor complex 3 / neuron projection regeneration / adrenomedullin receptor activity / adrenomedullin receptor complex / adrenomedullin receptor signaling pathway / amylin receptor activity / calcitonin receptor activity / spongiotrophoblast layer development / vascular associated smooth muscle cell proliferation / calcitonin gene-related peptide receptor activity / amylin receptor signaling pathway / Calcitonin-like ligand receptors / branching involved in labyrinthine layer morphogenesis / positive regulation of vasculogenesis / regulation of systemic arterial blood pressure / regulation of the force of heart contraction / G protein-coupled receptor internalization / regulation of urine volume / negative regulation of vascular permeability / negative regulation of vasoconstriction / positive regulation of heart rate / positive regulation of receptor recycling / response to starvation / odontogenesis of dentin-containing tooth / positive regulation of protein kinase A signaling / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / PKA activation in glucagon signalling / response to amyloid-beta / cAMP-mediated signaling / hair follicle placode formation / androgen metabolic process / intracellular transport / D1 dopamine receptor binding / developmental growth / vasculogenesis / animal organ regeneration / 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 / cellular response to hormone stimulus / positive regulation of vascular associated smooth muscle cell proliferation / activation of adenylate cyclase activity / adenylate cyclase activator activity / trans-Golgi network membrane / cellular response to estradiol stimulus / neural tube closure / female pregnancy / G protein-coupled receptor activity / protein localization to plasma membrane / positive regulation of protein localization to plasma membrane / intracellular protein transport / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / response to insulin / 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 / 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 / receptor internalization / ADP signalling through P2Y purinoceptor 12 / 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 / platelet aggregation / cognition / Glucagon-type ligand receptors / 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 Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.4 Å | ||||||||||||||||||
Authors | Belousoff MJ / Liang YL / Sexton P / Danev R | ||||||||||||||||||
Funding support | Australia, Japan, 5 items
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Citation | Journal: ACS Pharmacol Transl Sci / Year: 2020 Title: Structure and Dynamics of Adrenomedullin Receptors AM and AM Reveal Key Mechanisms in the Control of Receptor Phenotype by Receptor Activity-Modifying Proteins. Authors: Yi-Lynn Liang / Matthew J Belousoff / Madeleine M Fletcher / Xin Zhang / Maryam Khoshouei / Giuseppe Deganutti / Cassandra Koole / Sebastian G B Furness / Laurence J Miller / Debbie L Hay / ...Authors: Yi-Lynn Liang / Matthew J Belousoff / Madeleine M Fletcher / Xin Zhang / Maryam Khoshouei / Giuseppe Deganutti / Cassandra Koole / Sebastian G B Furness / Laurence J Miller / Debbie L Hay / Arthur Christopoulos / Christopher A Reynolds / Radostin Danev / Denise Wootten / Patrick M Sexton / Abstract: Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) receptors are critically important for metabolism, vascular tone, and inflammatory response. AM receptors are also required for normal ...Adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) receptors are critically important for metabolism, vascular tone, and inflammatory response. AM receptors are also required for normal lymphatic and blood vascular development and angiogenesis. They play a pivotal role in embryo implantation and fertility and can provide protection against hypoxic and oxidative stress. CGRP and AM receptors are heterodimers of the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) (CGRPR), as well as RAMP2 or RAMP3 (AMR and AMR, respectively). However, the mechanistic basis for RAMP modulation of CLR phenotype is unclear. In this study, we report the cryo-EM structure of the AMR in complex with AM and Gs at a global resolution of 3.0 Å, and structures of the AMR in complex with either AM or intermedin/adrenomedullin 2 (AM2) and Gs at 2.4 and 2.3 Å, respectively. The structures reveal distinctions in the primary orientation of the extracellular domains (ECDs) relative to the receptor core and distinct positioning of extracellular loop 3 (ECL3) that are receptor-dependent. Analysis of dynamic data present in the cryo-EM micrographs revealed additional distinctions in the extent of mobility of the ECDs. Chimeric exchange of the linker region of the RAMPs connecting the TM helix and the ECD supports a role for this segment in controlling receptor phenotype. Moreover, a subset of the motions of the ECD appeared coordinated with motions of the G protein relative to the receptor core, suggesting that receptor ECD dynamics could influence G protein interactions. This work provides fundamental advances in our understanding of GPCR function and how this can be allosterically modulated by accessory proteins. | ||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_20901.map.gz | 9 MB | EMDB map data format | |
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Header (meta data) | emd-20901-v30.xml emd-20901.xml | 31.5 KB 31.5 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_20901_fsc.xml | 10.2 KB | Display | FSC data file |
Images | emd_20901.png | 37.8 KB | ||
Masks | emd_20901_msk_1.map | 91.1 MB | Mask map | |
Others | emd_20901_additional_1.map.gz emd_20901_additional_2.map.gz emd_20901_additional_3.map.gz emd_20901_half_map_1.map.gz emd_20901_half_map_2.map.gz | 71.5 MB 50.7 MB 3.3 MB 71.7 MB 71.7 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-20901 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20901 | HTTPS FTP |
-Related structure data
Related structure data | 6uusMC 6uunC 6uvaC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_20901.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Annotation | Adrenomedullin 2 receptor G protein complex with adrenomedullin peptide Post Processed MAP | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Mask #1
File | emd_20901_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Additional map: Adrenomedullin 2 receptor G protein complex with adrenomedullin...
File | emd_20901_additional_1.map | ||||||||||||
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Annotation | Adrenomedullin 2 receptor G protein complex with adrenomedullin peptide unprocessed MAP for whole complex | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Adrenomedullin 2 receptor G protein complex with adrenomedullin...
File | emd_20901_additional_2.map | ||||||||||||
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Annotation | Adrenomedullin 2 receptor G protein complex with adrenomedullin peptide | ||||||||||||
Projections & Slices |
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Density Histograms |
-Additional map: Adrenomedullin 2 receptor G protein complex with adrenomedullin...
File | emd_20901_additional_3.map | ||||||||||||
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Annotation | Adrenomedullin 2 receptor G protein complex with adrenomedullin peptide focused refined map on receptor only which has been post-processed | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Adrenomedullin 2 receptor G protein complex with adrenomedullin...
File | emd_20901_half_map_1.map | ||||||||||||
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Annotation | Adrenomedullin 2 receptor G protein complex with adrenomedullin peptide | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Adrenomedullin 2 receptor G protein complex with adrenomedullin...
File | emd_20901_half_map_2.map | ||||||||||||
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Annotation | Adrenomedullin 2 receptor G protein complex with adrenomedullin peptide | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
+Entire : AM2:CLR:RAMP3:GasDN:Gb1:Gg2:Nb35 GPCR Complex
+Supramolecule #1: AM2:CLR:RAMP3:GasDN:Gb1:Gg2:Nb35 GPCR Complex
+Supramolecule #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
+Supramolecule #3: Nanobody 35
+Supramolecule #4: ADM
+Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #4: Nanobody 35
+Macromolecule #5: ADM
+Macromolecule #6: Calcitonin gene-related peptide type 1 receptor
+Macromolecule #7: Receptor activity-modifying protein 3
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 4 mg/mL |
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Buffer | pH: 7.4 |
Grid | Support film - Material: CARBON / Support film - topology: HOLEY ARRAY / Details: unspecified |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELDBright-field microscopy |
Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 68.0 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |