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- EMDB-28758: Calcitonin Receptor in complex with Gs and Pramlintide analogue p... -
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Open data
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Basic information
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Title | Calcitonin Receptor in complex with Gs and Pramlintide analogue peptide San45 | |||||||||||||||||||||||||||
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![]() | GPCR / calcitonin receptor / dual amylin and calcitonin receptor agonists / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||||||||||||||
Function / homology | ![]() calcitonin binding / amylin receptor complex 1 / amylin receptor complex 2 / 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 binding / amylin receptor complex 1 / amylin receptor complex 2 / 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 / 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 / positive regulation of calcium-mediated signaling / beta-2 adrenergic receptor binding / adenylate cyclase-activating adrenergic receptor signaling pathway / response to glucocorticoid / regulation of mRNA stability / activation of adenylate cyclase activity / adenylate cyclase activator activity / ossification / osteoclast differentiation / acrosomal vesicle / trans-Golgi network membrane / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / bone development / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / cognition / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / cilium / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / platelet aggregation / 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 / 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 / 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 / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / cell surface receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / G protein-coupled receptor signaling pathway / lysosomal membrane / axon Similarity search - Function | |||||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() | |||||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.0 Å | |||||||||||||||||||||||||||
![]() | Cao J / Sexton PM / Wootten DL / Belousoff MJ | |||||||||||||||||||||||||||
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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 116.4 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 27 KB 27 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 11.3 KB | Display | ![]() |
Images | ![]() | 28.5 KB | ||
Masks | ![]() | 125 MB | ![]() | |
Filedesc metadata | ![]() | 7.5 KB | ||
Others | ![]() ![]() ![]() | 3.3 MB 98.8 MB 98.8 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
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Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 18.5 KB | Display | |
Data in CIF | ![]() | 24.3 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8f0jMC ![]() 8f0kC ![]() 8f2aC ![]() 8f2bC C: citing same article ( M: atomic model generated by this map |
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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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Voxel size | X=Y=Z: 0.65 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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Density Histograms |
-Additional map: local refinement for receptor region
File | emd_28758_additional_1.map | ||||||||||||
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Annotation | local refinement for receptor region | ||||||||||||
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Density Histograms |
-Half map: #2
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Density Histograms |
-Half map: #1
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Density Histograms |
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Sample components
+Entire : calcitonin receptor in complex with Gs protein and San45 peptide
+Supramolecule #1: calcitonin receptor in complex with Gs protein and San45 peptide
+Macromolecule #1: pramlintide analogue San45
+Macromolecule #2: Calcitonin receptor
+Macromolecule #3: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
+Macromolecule #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+Macromolecule #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+Macromolecule #6: nanobody 35
+Macromolecule #7: N-hexadecanoyl-L-glutamic acid
+Macromolecule #8: 2-acetamido-2-deoxy-beta-D-glucopyranose
+Macromolecule #9: PHOSPHATIDYLETHANOLAMINE
+Macromolecule #10: PALMITIC ACID
+Macromolecule #11: CHOLESTEROL HEMISUCCINATE
+Macromolecule #12: (2S)-2-{[(1R)-1-hydroxyhexadecyl]oxy}-3-{[(1R)-1-hydroxyoctadecyl...
+Macromolecule #13: 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 KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 40.1 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.5 µm / Nominal defocus min: 0.2 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL / Protocol: AB INITIO MODEL / Overall B value: 44 |
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Output model | ![]() PDB-8f0j: |