Cryo-EM of GLP-1 receptor bound to GLP-1 and Gs protein
Zhang X, Belousoff MJ, Zhao P, Kooistra AJ, Truong TT, Ang SY, Underwood CR, Egebjerg T, Šenel P, Stewart GD, Liang YL, Glukhova A, Venugopal H, Christopoulos A, Furness SGB, Miller LJ, Reedtz-Runge S, Langmead CJ, Gloriam DE, Danev R, Sexton PM, Wootten D
Mol Cell (2020) 80 pp. 485-500.e7 [ DOI: 10.1016/j.molcel.2020.09.020 Pubmed: 33027691 ]
Image sets:
GLP-1 peptide hormone bound to Glucagon-Like peptide-1 (GLP-1) Receptor
Resolution: 2.1 Å
EM Method: Single-particle
Fitted PDBs: 6x18
Q-score: 0.563
Zhang X, Belousoff MJ, Zhao P, Kooistra AJ, Truong TT, Ang SY, Underwood CR, Egebjerg T, Senel P, Stewart GD, Liang YL, Glukhova A, Venugopal H, Christopoulos A, Furness SGB, Miller LJ, Reedtz-Runge S, Langmead CJ, Gloriam DE, Danev R, Sexton PM, Wootten D
Mol Cell (2020) 80 pp. 485- [ Pubmed: 33027691 DOI: doi:10.1016/j.molcel.2020.09.020 ]
- Glp-1 peptide hormone bound to glucagon-like peptide-1 (glp-1) receptor (120 kDa, Complex)
- Guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2 (6 kDa, Protein from Homo sapiens)
- Glucagon (3 kDa, Protein from Homo sapiens)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short (45 kDa, Protein from Homo sapiens)
- Nanobody 35 (Complex from Lama glama)
- Water (18 Da, Ligand)
- Glucagon-like peptide 1 receptor (56 kDa, Protein from Homo sapiens)
- Guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1 (37 kDa, Protein from Homo sapiens)
- Nanobody35 (13 kDa, Protein from Lama glama)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short, guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1, guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2, glucagon-like peptide 1 receptor (Complex from Homo sapiens)
Non peptide agonist CHU-128, bound to Glucagon-Like peptide-1 (GLP-1) Receptor
Resolution: 2.1 Å
EM Method: Single-particle
Fitted PDBs: 6x19
Q-score: 0.579
Zhang X, Belousoff MJ, Zhao P, Kooistra AJ, Truong TT, Ang SY, Underwood CR, Egebjerg T, Senel P, Stewart GD, Liang YL, Glukhova A, Venugopal H, Christopoulos A, Furness SGB, Miller LJ, Reedtz-Runge S, Langmead CJ, Gloriam DE, Danev R, Sexton PM, Wootten D
Mol Cell (2020) 80 pp. 485- [ Pubmed: 33027691 DOI: doi:10.1016/j.molcel.2020.09.020 ]
- Guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2 (6 kDa, Protein from Homo sapiens)
- Water (18 Da, Ligand)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short (45 kDa, Protein from Homo sapiens)
- Nanobody35 (Complex from Lama glama)
- Glucagon-like peptide 1 receptor (56 kDa, Protein from Homo sapiens)
- 3-{(1s)-1-[5-(2,2-dimethylmorpholin-4-yl)-2-{(4s)-2-(4-fluoro-3,5-dimethylphenyl)-3-[3-(4-fluoro-1-methyl-1h-indazol-5-yl)-2-oxo-2,3-dihydro-1h-imidazol-1-yl]-4-methyl-2,4,6,7-tetrahydro-5h-pyrazolo[4,3-c]pyridine-5-carbonyl}-1h-indol-1-yl]butyl}-1,2,4-oxadiazol-5(4h)-one (885 Da, Ligand)
- Chu-128:glp-1r:gs complex (120 kDa, Complex)
- Guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1 (37 kDa, Protein from Homo sapiens)
- Nanobody35 (13 kDa, Protein from Lama glama)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short, guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1, guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2, glucagon-like peptide 1 receptor (Complex from Homo sapiens)
Non peptide agonist PF-06882961, bound to Glucagon-Like peptide-1 (GLP-1) Receptor
Resolution: 2.5 Å
EM Method: Single-particle
Fitted PDBs: 6x1a
Q-score: 0.522
Zhang X, Belousoff MJ, Zhao P, Kooistra AJ, Truong TT, Ang SY, Underwood CR, Egebjerg T, Senel P, Stewart GD, Liang YL, Glukhova A, Venugopal H, Christopoulos A, Furness SGB, Miller LJ, Reedtz-Runge S, Langmead CJ, Gloriam DE, Danev R, Sexton PM, Wootten D
Mol Cell (2020) 80 pp. 485- [ Pubmed: 33027691 DOI: doi:10.1016/j.molcel.2020.09.020 ]
- Pf-06882961:glp-1r:gs complex (120 kDa, Complex)
- Guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2 (6 kDa, Protein from Homo sapiens)
- Water (18 Da, Ligand)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short (45 kDa, Protein from Homo sapiens)
- 2-[(4-{6-[(4-cyano-2-fluorophenyl)methoxy]pyridin-2-yl}piperidin-1-yl)methyl]-1-{[(2s)-oxetan-2-yl]methyl}-1h-benzimidazole-6-carboxylic acid (555 Da, Ligand)
- Nanobody35 (Complex from Lama glama)
- Glucagon-like peptide 1 receptor (56 kDa, Protein from Homo sapiens)
- Guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1 (37 kDa, Protein from Homo sapiens)
- Nanobody35 (13 kDa, Protein from Lama glama)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short, guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1, guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2, glucagon-like peptide 1 receptor (Complex from Homo sapiens)
Human secretin receptor Gs complex
Resolution: 4.3 Å
EM Method: Single-particle
Fitted PDBs: 6wi9
Q-score: 0.359
Dong M, Deganutti G, Piper SJ, Liang YL, Khoshouei M, Belousoff MJ, Harikumar KG, Reynolds CA, Glukhova A, Furness SGB, Christopoulos A, Danev R, Wootten D, Sexton PM, Miller LJ
Nat Commun (2020) 11 pp. 4137-4137 [ Pubmed: 32811827 DOI: doi:10.1038/s41467-020-17791-4 ]
- Secretin (Complex from Homo sapiens)
- Guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1 (37 kDa, Protein from Homo sapiens)
- Nanobody35 (15 kDa, Protein from Lama glama)
- Secretin (3 kDa, Protein from Homo sapiens)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short (45 kDa, Protein from Homo sapiens)
- Gs coupled sectretin complex with secretin peptide (Complex)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short, guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1, guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2, secretin receptor (Complex from Homo sapiens)
- Nanobody35 (Complex from Lama glama)
- Guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2 (7 kDa, Protein from Homo sapiens)
- Secretin receptor (51 kDa, Protein from Homo sapiens)
Human secretin receptor Gs complex
Resolution: 2.3 Å
EM Method: Single-particle
Fitted PDBs: 6wzg
Q-score: 0.609
Dong M, Deganutti G, Piper SJ, Liang YL, Khoshouei M, Belousoff MJ, Harikumar KG, Reynolds CA, Glukhova A, Furness SGB, Christopoulos A, Danev R, Wootten D, Sexton PM, Miller LJ
Nat Commun (2020) 11 pp. 4137-4137 [ Pubmed: 32811827 DOI: doi:10.1038/s41467-020-17791-4 ]
- Secretin (Complex from Homo sapiens)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short (45 kDa, Protein from Homo sapiens)
- Guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1 (37 kDa, Protein from Homo sapiens)
- Nanobody35 (15 kDa, Protein from Lama glama)
- Secretin (3 kDa, Protein from Homo sapiens)
- Gs coupled secretin complex with secretin peptide (Complex)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short, guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1, guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2, secretin receptor (Complex from Homo sapiens)
- Nanobody35 (Complex from Lama glama)
- Guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2 (7 kDa, Protein from Homo sapiens)
- Secretin receptor (51 kDa, Protein from Homo sapiens)
Resolution: 2.4 Å
EM Method: Single-particle
Fitted PDBs: 6uus
Q-score: 0.535
Liang YL, Belousoff MJ, Fletcher MM, Zhang X, Khoshouei M, Deganutti G, Koole C, Furness SGB, Miller LJ, Hay DL, Christopoulos A, Reynolds CA, Danev R, Wootten D, Sexton PM
Acs Pharmacol Transl Sci (2020) 3 pp. 263-284 [ Pubmed: 32296767 DOI: doi:10.1021/acsptsci.9b00080 ]
- Am2:clr:ramp3:gasdn:gb1:gg2:nb35 gpcr complex (Complex)
- Nanobody 35 (15 kDa, Protein from Lama glama)
- Receptor activity-modifying protein 3 (16 kDa, Protein from Homo sapiens)
- Adm (Complex from Homo sapiens)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short (45 kDa, Protein from Homo sapiens)
- Nanobody 35 (Complex from Lama glama)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short, guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1, receptor activity-modifying protein 3, guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2, calcitonin gene-related peptide type 1 receptor (Complex from Homo sapiens)
- Calcitonin gene-related peptide type 1 receptor (56 kDa, Protein from Homo sapiens)
- Guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2 (7 kDa, Protein from Homo sapiens)
- Adm (6 kDa, Protein from Homo sapiens)
- Guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1 (38 kDa, Protein from Homo sapiens)
Resolution: 2.3 Å
EM Method: Single-particle
Fitted PDBs: 6uva
Q-score: 0.553
Liang YL, Belousoff MJ, Fletcher MM, Zhang X, Khoshouei M, Deganutti G, Koole C, Furness SGB, Miller LJ, Hay DL, Christopoulos A, Reynolds CA, Danev R, Wootten D, Sexton PM
Acs Pharmacol Transl Sci (2020) 3 pp. 263-284 [ Pubmed: 32296767 DOI: doi:10.1021/acsptsci.9b00080 ]
- Am2:clr:ramp3:gasdn:gb1:gg2:nb35 gpcr complex (Complex)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short (45 kDa, Protein from Homo sapiens)
- Nanobody 35 (15 kDa, Protein from Lama glama)
- Receptor activity-modifying protein 3 (16 kDa, Protein from Homo sapiens)
- Nanobody 35 (Complex from Lama glama)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short, guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1, receptor activity-modifying protein 3, guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2, calcitonin gene-related peptide type 1 receptor (Complex from Homo sapiens)
- Calcitonin gene-related peptide type 1 receptor (56 kDa, Protein from Homo sapiens)
- Protein adm2 (Complex from Homo sapiens)
- Guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2 (7 kDa, Protein from Homo sapiens)
- Guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1 (38 kDa, Protein from Homo sapiens)
- Protein adm2 (5 kDa, Protein from Homo sapiens)
Resolution: 3.0 Å
EM Method: Single-particle
Fitted PDBs: 6uun
Q-score: 0.48
Liang YL, Belousoff MJ, Fletcher MM, Zhang X, Khoshouei M, Deganutti G, Koole C, Furness SGB, Miller LJ, Hay DL, Christopoulos A, Reynolds CA, Danev R, Wootten D, Sexton PM
Acs Pharmacol Transl Sci (2020) 3 pp. 263-284 [ Pubmed: 32296767 DOI: doi:10.1021/acsptsci.9b00080 ]
- Receptor activity-modifying protein 2 (17 kDa, Protein from Homo sapiens)
- Guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2 (7 kDa, Protein from Homo sapiens)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short, guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1, receptor activity-modifying protein 2, guanine nucleotide-binding protein g(i)/g(s)/g(o) subunit gamma-2, calcitonin gene-related peptide type 1 receptor (Complex from Homo sapiens)
- Am:clr:ramp2:gasdn:gb1:gg2:nb35 gpcr complex (Complex)
- Adm (6 kDa, Protein from Homo sapiens)
- Adm (Complex from Homo sapiens)
- Guanine nucleotide-binding protein g(s) subunit alpha isoforms short (45 kDa, Protein from Homo sapiens)
- Nanobody 35 (Complex from Lama glama)
- Guanine nucleotide-binding protein g(i)/g(s)/g(t) subunit beta-1 (38 kDa, Protein from Homo sapiens)
- Calcitonin gene-related peptide type 1 receptor (56 kDa, Protein from Homo sapiens)
- Nanobody 35 (15 kDa, Protein from Lama glama)
Cryo-EM of GLP-1 receptor bound to TT-OAD2 non-peptidic agonist
Zhao P, Liang YL, Belousoff MJ, Deganutti G, Fletcher MM, Willard FS, Bell MG, Christe ME, Sloop KW, Inoue A, Truong TT, Clydesdale L, Furness SGB, Christopoulos A, Wang MW, Miller LJ, Reynolds CA, Danev R, Sexton PM, Wootten D
Nature (2020) 577 pp. 432-436 [ DOI: 10.1038/s41586-019-1902-z Pubmed: 31915381 ]
Image sets: