[English] 日本語
Yorodumi- EMDB-22882: Semaglutide-bound Glucagon-Like Peptide-1 (GLP-1) Receptor in Com... -
+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-22882 | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Title | Semaglutide-bound Glucagon-Like Peptide-1 (GLP-1) Receptor in Complex with Gs protein | ||||||||||||||||||
Map data | consensus postprocess map | ||||||||||||||||||
Sample |
| ||||||||||||||||||
Function / homology | Function and homology information glucagon-like peptide 1 receptor activity / glucagon receptor activity / hormone secretion / positive regulation of blood pressure / post-translational protein targeting to membrane, translocation / regulation of heart contraction / activation of adenylate cyclase activity / response to psychosocial stress / peptide hormone binding / cAMP-mediated signaling ...glucagon-like peptide 1 receptor activity / glucagon receptor activity / hormone secretion / positive regulation of blood pressure / post-translational protein targeting to membrane, translocation / regulation of heart contraction / activation of adenylate cyclase activity / response to psychosocial stress / peptide hormone binding / cAMP-mediated signaling / negative regulation of blood pressure / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to prostaglandin E stimulus / transmembrane signaling receptor activity / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / 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 / learning or memory / cell surface receptor signaling pathway / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / signal transduction / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | Homo sapiens (human) / Lama glama (llama) / synthetic construct (others) | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.5 Å | ||||||||||||||||||
Authors | Zhang X / Belousoff MJ / Danev R / Sexton PM / Wootten D | ||||||||||||||||||
Funding support | Australia, Japan, 5 items
| ||||||||||||||||||
Citation | Journal: Cell Rep / Year: 2021 Title: Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes. Authors: Xin Zhang / Matthew J Belousoff / Yi-Lynn Liang / Radostin Danev / Patrick M Sexton / Denise Wootten / Abstract: The glucagon-like peptide-1 receptor (GLP-1R) regulates insulin secretion, carbohydrate metabolism, and appetite and is an important target for treatment of type 2 diabetes and obesity. Multiple GLP- ...The glucagon-like peptide-1 receptor (GLP-1R) regulates insulin secretion, carbohydrate metabolism, and appetite and is an important target for treatment of type 2 diabetes and obesity. Multiple GLP-1R agonists have entered into clinical trials, with some, such as semaglutide, progressing to approval. Others, including taspoglutide, failed due to the high incidence of side effects or insufficient efficacy. GLP-1R agonists have a broad spectrum of signaling profiles, but molecular understanding is limited by a lack of structural information on how different agonists engage with the GLP-1R. Here, we report cryoelectron microscopy (cryo-EM) structures and cryo-EM 3D variability analysis of semaglutide- and taspoglutide-bound GLP-1R-Gs protein complexes. These reveal similar peptide interactions to GLP-1 but different motions within the receptor and bound peptides, providing insights into the molecular determinants of GLP-1R peptide engagement. | ||||||||||||||||||
History |
|
-Structure visualization
Movie |
Movie viewer |
---|---|
Structure viewer | EM map: SurfViewMolmilJmol/JSmol |
Supplemental images |
-Downloads & links
-EMDB archive
Map data | emd_22882.map.gz | 85.3 MB | EMDB map data format | |
---|---|---|---|---|
Header (meta data) | emd-22882-v30.xml emd-22882.xml | 25.3 KB 25.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_22882_fsc.xml | 10.2 KB | Display | FSC data file |
Images | emd_22882.png | 122 KB | ||
Masks | emd_22882_msk_1.map | 91.1 MB | Mask map | |
Others | emd_22882_additional_1.map.gz emd_22882_additional_2.map.gz emd_22882_half_map_1.map.gz emd_22882_half_map_2.map.gz | 70.8 MB 78.8 MB 71.4 MB 71.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-22882 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22882 | HTTPS FTP |
-Validation report
Summary document | emd_22882_validation.pdf.gz | 731.9 KB | Display | EMDB validaton report |
---|---|---|---|---|
Full document | emd_22882_full_validation.pdf.gz | 731.4 KB | Display | |
Data in XML | emd_22882_validation.xml.gz | 17.3 KB | Display | |
Data in CIF | emd_22882_validation.cif.gz | 22.8 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22882 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22882 | HTTPS FTP |
-Related structure data
Related structure data | 7ki0MC 7ki1C M: atomic model generated by this map C: citing same article (ref.) |
---|---|
Similar structure data |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
---|---|
Related items in Molecule of the Month |
-Map
File | Download / File: emd_22882.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | consensus postprocess map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.83 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
|
-Supplemental data
-Mask #1
File | emd_22882_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: consensus refinement map
File | emd_22882_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | consensus refinement map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Additional map: receptor ECD-focused postprocess map that is resampled to...
File | emd_22882_additional_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | receptor ECD-focused postprocess map that is resampled to the consensus map | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: consensus half map1
File | emd_22882_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | consensus half map1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Half map: consensus half map1
File | emd_22882_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Annotation | consensus half map1 | ||||||||||||
Projections & Slices |
| ||||||||||||
Density Histograms |
-Sample components
-Entire : Semaglutide-GLP-1R-Gs complex
Entire | Name: Semaglutide-GLP-1R-Gs complex |
---|---|
Components |
|
-Supramolecule #1: Semaglutide-GLP-1R-Gs complex
Supramolecule | Name: Semaglutide-GLP-1R-Gs complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#6 |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
-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: Homo sapiens (human) |
Molecular weight | Theoretical: 45.699434 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
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: Homo sapiens (human) |
Molecular weight | Theoretical: 37.413863 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: QSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...String: QSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA 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: Homo sapiens (human) |
Molecular weight | Theoretical: 6.375332 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: NTASIAQARK LVEQLKMEAN IDRIKVSKAA ADLMAYCEAH AKEDPLLTPV PASENPFR |
-Macromolecule #4: Nb35
Macromolecule | Name: Nb35 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Lama glama (llama) |
Molecular weight | Theoretical: 13.885439 KDa |
Recombinant expression | Organism: Escherichia coli (E. coli) |
Sequence | String: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSS |
-Macromolecule #5: Semaglutide
Macromolecule | Name: Semaglutide / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: synthetic construct (others) |
Molecular weight | Theoretical: 3.40174 KDa |
Sequence | String: H(AIB)EGTFTSDV SSYLEGQAAK EFIAWLVRGR G |
-Macromolecule #6: Glucagon-like peptide 1 receptor
Macromolecule | Name: Glucagon-like peptide 1 receptor / type: protein_or_peptide / ID: 6 / Number of copies: 1 / Enantiomer: LEVO |
---|---|
Source (natural) | Organism: Homo sapiens (human) |
Molecular weight | Theoretical: 56.748418 KDa |
Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
Sequence | String: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PARPQGATVS LWETVQKWRE YRRQCQRSLT EDPPPATDLF CNRTFDEYAC WPDGEPGSF VNVSCPWYLP WASSVPQGHV YRFCTAEGLW LQKDNSSLPW RDLSECEESK RGERSSPEEQ LLFLYIIYTV G YALSFSAL ...String: MKTIIALSYI FCLVFADYKD DDDLEVLFQG PARPQGATVS LWETVQKWRE YRRQCQRSLT EDPPPATDLF CNRTFDEYAC WPDGEPGSF VNVSCPWYLP WASSVPQGHV YRFCTAEGLW LQKDNSSLPW RDLSECEESK RGERSSPEEQ LLFLYIIYTV G YALSFSAL VIASAILLGF RHLHCTRNYI HLNLFASFIL RALSVFIKDA ALKWMYSTAA QQHQWDGLLS YQDSLSCRLV FL LMQYCVA ANYYWLLVEG VYLYTLLAFS VFSEQWIFRL YVSIGWGVPL LFVVPWGIVK YLYEDEGCWT RNSNMNYWLI IRL PILFAI GVNFLIFVRV ICIVVSKLKA NLMCKTDIKC RLAKSTLTLI PLLGTHEVIF AFVMDEHARG TLRFIKLFTE LSFT SFQGL MVAILYCFVN NEVQLEFRKS WERWRLEHLH IQRDSSMKPL KCPTSSLSSG ATAGSSMYTA TCQASCSPAG LEVLF QGPH HHHHHHH |
-Macromolecule #7: 17-amino-10-oxo-3,6,12,15-tetraoxa-9-azaheptadecan-1-oic acid
Macromolecule | Name: 17-amino-10-oxo-3,6,12,15-tetraoxa-9-azaheptadecan-1-oic acid type: ligand / ID: 7 / Number of copies: 1 / Formula: WF1 |
---|---|
Molecular weight | Theoretical: 308.328 Da |
Chemical component information | ChemComp-WF1: |
-Macromolecule #8: water
Macromolecule | Name: water / type: ligand / ID: 8 / Number of copies: 79 / Formula: HOH |
---|---|
Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-Experimental details
-Structure determination
Method | cryo EM |
---|---|
Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Buffer | pH: 7.4 |
---|---|
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
---|---|
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average exposure time: 2.996 sec. / Average electron dose: 0.887 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |