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Yorodumi- EMDB-47447: Glucagon Like Peptide Receptor-1 (GLP1R) A316T mutant with GLP-1 ... -
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Open data
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Basic information
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| Title | Glucagon Like Peptide Receptor-1 (GLP1R) A316T mutant with GLP-1 peptide. Dominant negative Gs complex. | ||||||||||||
Map data | B-factor sharpened Consensus map | ||||||||||||
Sample |
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Keywords | GPCR / GLP1 / GLP-1R / MEMBRANE PROTEIN | ||||||||||||
| Function / homology | Function and homology informationglucagon receptor binding / glucagon-like peptide 1 receptor activity / glucagon receptor activity / : / positive regulation of blood pressure / hormone secretion / post-translational protein targeting to membrane, translocation / feeding behavior / negative regulation of execution phase of apoptosis / response to psychosocial stress ...glucagon receptor binding / glucagon-like peptide 1 receptor activity / glucagon receptor activity / : / positive regulation of blood pressure / hormone secretion / post-translational protein targeting to membrane, translocation / feeding behavior / negative regulation of execution phase of apoptosis / response to psychosocial stress / positive regulation of calcium ion import / regulation of heart contraction / regulation of insulin secretion / adenylate cyclase-activating G protein-coupled bile acid receptor signaling pathway / adenylate cyclase-activating serotonin receptor signaling pathway / peptide hormone binding / regulation of skeletal muscle contraction / Synthesis, secretion, and deacylation of Ghrelin / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / intracellular transport / D1 dopamine receptor binding / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / Hedgehog 'off' state / activation of adenylate cyclase activity / cellular response to acidic pH / adenylate cyclase-activating adrenergic receptor signaling pathway / negative regulation of blood pressure / cellular response to glucagon stimulus / positive regulation of gluconeogenesis / intracellular glucose homeostasis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / adenylate cyclase activator activity / response to activity / trans-Golgi network membrane / gluconeogenesis / negative regulation of inflammatory response to antigenic stimulus / response to prostaglandin E / hormone activity / bone development / platelet aggregation / cognition / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / positive regulation of insulin secretion / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / sensory perception of smell / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / transmembrane signaling receptor activity / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / cellular response to prostaglandin E stimulus / glucose homeostasis / G alpha (12/13) signalling events / heterotrimeric G-protein complex / positive regulation of cold-induced thermogenesis / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / extracellular vesicle / sensory perception of taste / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / positive regulation of cytosolic calcium ion concentration / retina development in camera-type eye / GTPase binding / G protein activity / fibroblast proliferation / Ca2+ pathway / secretory granule lumen / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events Similarity search - Function | ||||||||||||
| Biological species | Homo sapiens (human) / ![]() | ||||||||||||
| Method | single particle reconstruction / cryo EM / Resolution: 3.3 Å | ||||||||||||
Authors | Deane-Alder K / Belousoff MJ / Wootten DL | ||||||||||||
| Funding support | Australia, 3 items
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Citation | Journal: Sci Adv / Year: 2026Title: In vivo functional profiling and structural characterization of the human A316T variant. Authors: Liliane El Eid / Yusman Manchanda / Gregory Austin / Kieran Deane-Alder / Roxana-Maria Rujan / Zamara Mariam / Affiong I Oqua / Matthew J Belousoff / Jorge Bernardino de la Serna / Kyle W ...Authors: Liliane El Eid / Yusman Manchanda / Gregory Austin / Kieran Deane-Alder / Roxana-Maria Rujan / Zamara Mariam / Affiong I Oqua / Matthew J Belousoff / Jorge Bernardino de la Serna / Kyle W Sloop / Guy A Rutter / Alex Montoya / Dominic J Withers / Steven J Millership / Karim Bouzakri / Ben Jones / Christopher A Reynolds / Patrick M Sexton / Denise Wootten / Giuseppe Deganutti / Alejandra Tomas / ![]() Abstract: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective therapies for type 2 diabetes (T2D) and obesity, yet patient responses are variable, with gene variation potentially linked to ...Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective therapies for type 2 diabetes (T2D) and obesity, yet patient responses are variable, with gene variation potentially linked to therapeutic outcomes. A natural missense variant, A316T, protects against T2D and cardiovascular disease. Here, we generated and characterized a human A316T mouse model. Human mice displayed lower fasting blood glucose versus wild-type littermates even under metabolic stress, as well as slower weight gain and alterations in islet cytoarchitecture, glucagon secretion, and liver metabolism under a high-fat, high-sucrose diet. This was however associated with blunted responses to pharmacological GLP-1RAs in vivo. Further investigations in β cell models demonstrated that human A316T exhibits characteristics of constitutive activation but dampened GLP-1RA responses. Results are further supported by cryo-EM analyses and molecular dynamics simulations of GLP-1R A316T structure, collectively demonstrating that the A316T variant governs basal GLP-1R activity and pharmacological responses to GLP-1R-targeting therapies. | ||||||||||||
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Structure visualization
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Downloads & links
-EMDB archive
| Map data | emd_47447.map.gz | 47 MB | EMDB map data format | |
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| Header (meta data) | emd-47447-v30.xml emd-47447.xml | 29.8 KB 29.8 KB | Display Display | EMDB header |
| FSC (resolution estimation) | emd_47447_fsc.xml | 9.5 KB | Display | FSC data file |
| Images | emd_47447.png | 32 KB | ||
| Masks | emd_47447_msk_1.map | 91.1 MB | Mask map | |
| Filedesc metadata | emd-47447.cif.gz | 8 KB | ||
| Others | emd_47447_additional_1.map.gz emd_47447_half_map_1.map.gz emd_47447_half_map_2.map.gz | 45.3 MB 84.6 MB 84.6 MB | ||
| Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-47447 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-47447 | HTTPS FTP |
-Related structure data
| Related structure data | ![]() 9e2aMC M: atomic model generated by this map C: citing same article ( |
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| Similar structure data | Similarity search - Function & homology F&H Search |
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Links
| EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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| Related items in Molecule of the Month |
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Map
| File | Download / File: emd_47447.map.gz / Format: CCP4 / Size: 91.1 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| Annotation | B-factor sharpened Consensus map | ||||||||||||||||||||||||||||||||||||
| Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
| Voxel size | X=Y=Z: 0.86 Å | ||||||||||||||||||||||||||||||||||||
| Density |
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| Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
| Details | EMDB XML:
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-Supplemental data
-Mask #1
| File | emd_47447_msk_1.map | ||||||||||||
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-Additional map: Unsharpened Consensus map
| File | emd_47447_additional_1.map | ||||||||||||
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| Annotation | Unsharpened Consensus map | ||||||||||||
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-Half map: Half map 1
| File | emd_47447_half_map_1.map | ||||||||||||
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| Annotation | Half map 1 | ||||||||||||
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-Half map: half map 2
| File | emd_47447_half_map_2.map | ||||||||||||
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| Annotation | half map 2 | ||||||||||||
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Sample components
-Entire : GLP-1R ternary complex
| Entire | Name: GLP-1R ternary complex |
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| Components |
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-Supramolecule #1: GLP-1R ternary complex
| Supramolecule | Name: GLP-1R ternary complex / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all |
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| Source (natural) | Organism: Homo sapiens (human) |
-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 |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 45.683434 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 HYCYPHFTCA VDTENIRRVF NDCRDIIQRM HLRQYELL UniProtKB: 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 | 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 |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 38.534062 KDa |
| Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
| 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 UniProtKB: 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 | 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 |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 7.861143 KDa |
| Recombinant expression | Organism: Trichoplusia ni (cabbage looper) |
| Sequence | String: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-Macromolecule #4: Nanobody 35
| Macromolecule | Name: Nanobody 35 / type: protein_or_peptide / ID: 4 / Number of copies: 1 / Enantiomer: LEVO |
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| 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: Glucagon
| Macromolecule | Name: Glucagon / type: protein_or_peptide / ID: 5 / Number of copies: 1 / Enantiomer: LEVO |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 3.302648 KDa |
| Sequence | String: HAEGTFTSDV SSYLEGQAAK EFIAWLVKGR UniProtKB: Pro-glucagon |
-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 |
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| Source (natural) | Organism: Homo sapiens (human) |
| Molecular weight | Theoretical: 56.778441 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 PILFTI GVNFLIFVRV ICIVVSKLKA NLMCKTDIKC RLAKSTLTLI PLLGTHEVIF AFVMDEHARG TLRFIKLFTE LSFT SFQGL MVAILYCFVN NEVQLEFRKS WERWRLEHLH IQRDSSMKPL KCPTSSLSSG ATAGSSMYTA TCQASCSPAG LEVLF QGPH HHHHHHH UniProtKB: Glucagon-like peptide 1 receptor |
-Experimental details
-Structure determination
| Method | cryo EM |
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Processing | single particle reconstruction |
| Aggregation state | particle |
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Sample preparation
| Concentration | 4 mg/mL |
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| Buffer | pH: 7.4 |
| Grid | Model: Quantifoil R1.2/1.3 / Material: GOLD / Mesh: 200 / Support film - Material: GOLD / Support film - topology: HOLEY ARRAY |
| Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 277 K |
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Electron microscopy
| Microscope | TFS GLACIOS |
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| Image recording | Film or detector model: FEI FALCON IV (4k x 4k) / Digitization - Dimensions - Width: 4000 pixel / Digitization - Dimensions - Height: 4000 pixel / Average electron dose: 50.0 e/Å2 |
| Electron beam | Acceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN |
| Electron optics | C2 aperture diameter: 50.0 µm / Calibrated defocus min: 0.5 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.4000000000000001 µm / Nominal defocus min: 0.5 µm |
| Sample stage | Cooling holder cryogen: NITROGEN |
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About Yorodumi



Keywords
Homo sapiens (human)
Authors
Australia, 3 items
Citation


























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Trichoplusia ni (cabbage looper)
Processing
FIELD EMISSION GUN
