[English] 日本語
![](img/lk-miru.gif)
- EMDB-26184: Calcitonin Receptor in complex with Gs and rat amylin peptide, by... -
+
Open data
-
Basic information
Entry | ![]() | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Calcitonin Receptor in complex with Gs and rat amylin peptide, bypass motif | ||||||||||||||||||||||||
![]() | post-processed consensus refinement | ||||||||||||||||||||||||
![]() |
| ||||||||||||||||||||||||
Function / homology | ![]() Calcitonin-like ligand receptors / 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 ...Calcitonin-like ligand receptors / 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 / positive regulation of cAMP-mediated signaling / negative regulation of ossification / negative regulation of bone resorption / eating behavior / negative regulation of osteoclast differentiation / positive regulation of protein kinase A signaling / response to amyloid-beta / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / bone resorption / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / response to glucocorticoid / sensory perception of pain / regulation of mRNA stability / adenylate cyclase activator activity / positive regulation of calcium-mediated signaling / ossification / osteoclast differentiation / acrosomal vesicle / trans-Golgi network membrane / secretory granule / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / hormone activity / 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 / cognition / platelet aggregation / 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 / 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 / glucose metabolic process / 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 / Ca2+ pathway / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / amyloid-beta binding / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / positive regulation of ERK1 and ERK2 cascade Similarity search - Function | ||||||||||||||||||||||||
Biological species | ![]() ![]() ![]() ![]() ![]() | ||||||||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||||||||||||||
![]() | Cao J / Belousoff MJ / Johnson RM / Wootten DL / Sexton PM | ||||||||||||||||||||||||
Funding support | ![]() ![]()
| ||||||||||||||||||||||||
![]() | ![]() 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 | ![]() | 85 MB | ![]() | |
---|---|---|---|---|
Header (meta data) | ![]() ![]() | 34.8 KB 34.8 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.8 KB | Display | ![]() |
Images | ![]() | 27.3 KB | ||
Masks | ![]() | 91.1 MB | ![]() | |
Others | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() | 44 MB 81.5 MB 81.5 MB 43.7 MB 84.6 MB 45.4 MB 84.5 MB 84.5 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7tylMC ![]() 7tyfC ![]() 7tyhC ![]() 7tyiC ![]() 7tynC ![]() 7tyoC ![]() 7tywC ![]() 7tyxC ![]() 7tyyC ![]() 7tzfC C: citing same article ( M: atomic model generated by this map |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
EMDB pages | ![]() ![]() |
---|---|
Related items in Molecule of the Month |
-
Map
File | ![]() | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | post-processed consensus refinement | ||||||||||||||||||||
Voxel size | X=Y=Z: 0.856 Å | ||||||||||||||||||||
Density |
| ||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
|
-Supplemental data
-Mask #1
File | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: unfiltered consensus map
File | emd_26184_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | unfiltered consensus map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: sharpened combined composite map combining locally refined map
File | emd_26184_additional_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | sharpened combined composite map combining locally refined map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: unsharpened combined composite map combining locally refined maps
File | emd_26184_additional_3.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | unsharpened combined composite map combining locally refined maps | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: unsharpened local refinement map of the ECD
File | emd_26184_additional_4.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | unsharpened local refinement map of the ECD | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: sharpened local refinement map of the ECD
File | emd_26184_additional_5.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | sharpened local refinement map of the ECD | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: locally refinement on the receptor
File | emd_26184_additional_6.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | locally refinement on the receptor | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map 1
File | emd_26184_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map 1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: half map 2
File | emd_26184_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | half map 2 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-
Sample components
-Entire : Calcitonin Receptor in complex with Gs and rat amylin peptide, by...
Entire | Name: Calcitonin Receptor in complex with Gs and rat amylin peptide, bypass motif |
---|---|
Components |
|
-Supramolecule #1: Calcitonin Receptor in complex with Gs and rat amylin peptide, by...
Supramolecule | Name: Calcitonin Receptor in complex with Gs and rat amylin peptide, bypass motif type: complex / Chimera: Yes / ID: 1 / Parent: 0 / Macromolecule list: all |
---|
-Macromolecule #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Macromolecule | Name: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 45.699434 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE ...String: MGCLGNSKTE DQRNEEKAQR EANKKIEKQL QKDKQVYRAT HRLLLLGAGE SGKNTIVKQM RILHVNGFNG EGGEEDPQAA RSNSDGEKA TKVQDIKNNL KEAIETIVAA MSNLVPPVEL ANPENQFRVD YILSVMNVPD FDFPPEFYEH AKALWEDEGV R ACYERSNE YQLIDCAQYF LDKIDVIKQA DYVPSDQDLL RCRVLTSGIF ETKFQVDKVN FHMFDVGAQR DERRKWIQCF ND VTAIIFV VASSSYNMVI REDNQTNRLQ AALKLFDSIW NNKWLRDTSV ILFLNKQDLL AEKVLAGKSK IEDYFPEFAR YTT PEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCS VDTENIRRVF NDCRDIIQRM HLRQYELL |
-Macromolecule #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 38.534062 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...String: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWN |
-Macromolecule #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Macromolecule | Name: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 type: protein_or_peptide / ID: 3 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 7.861143 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L |
-Macromolecule #4: Nanobody 35
Macromolecule | Name: Nanobody 35 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 15.140742 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSH HHHHHEPEA |
-Macromolecule #5: amylin peptide
Macromolecule | Name: amylin peptide / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 3.924426 KDa |
Sequence | String: KCNTATCATQ RLANFLVRSS NNLGPVLPPT NVGSNTY(NH2) |
-Macromolecule #6: Calcitonin receptor
Macromolecule | Name: Calcitonin receptor / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 58.469594 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PAAFSNQTYP TIEPKPFLYV VGRKKMMDAQ YKCYDRMQQL PAYQGEGPYC NRTWDGWLC WDDTPAGVLS YQFCPDYFPD FDPSEKVTKY CDEKGVWFKH PENNRTWSNY TMCNAFTPEK LKNAYVLYYL A IVGHSLSI ...String: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PAAFSNQTYP TIEPKPFLYV VGRKKMMDAQ YKCYDRMQQL PAYQGEGPYC NRTWDGWLC WDDTPAGVLS YQFCPDYFPD FDPSEKVTKY CDEKGVWFKH PENNRTWSNY TMCNAFTPEK LKNAYVLYYL A IVGHSLSI FTLVISLGIF VFFRSLGCQR VTLHKNMFLT YILNSMIIII HLVEVVPNGE LVRRDPVSCK ILHFFHQYMM AC NYFWMLC EGIYLHTLIV VAVFTEKQRL RWYYLLGWGF PLVPTTIHAI TRAVYFNDNC WLSVETHLLY IIHGPVMAAL VVN FFFLLN IVRVLVTKMR ETHEAESHMY LKAVKATMIL VPLLGIQFVV FPWRPSNKML GKIYDYVMHS LIHFQGFFVA TIYC FCNNE VQTTVKRQWA QFKIQWNQRW GRRPSNRSAR AAAAAAEAGD IPIYICHQEL RNEPANNQGE ESAEIIPLNI IEQES SAPA GLEVLFQGPH HHHHHHH |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
![]() | single particle reconstruction |
Aggregation state | particle |
-
Sample preparation
Concentration | 13 mg/mL |
---|---|
Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE |
-
Electron microscopy
Microscope | TFS GLACIOS |
---|---|
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 |