8WG7: Peptide free and Gs-coupled GLP-1R

Cryo-EM structures of peptide free and Gs-coupled GLP-1R. Determined by electron microscopy at 2.54 Å resolution. Released 6 Mar 2024.

Method: Electron microscopy
Resolution: 2.54 Å
Organisms: Homo sapiens, Rattus norvegicus, Bos taurus
Chains: 5
Atoms: 8,123
Mol. weight: 158.52 kDa
Released: 6 Mar 2024

Explore 8WG7 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8WG7 contains 32 α-helices and 45 β-strands across 5 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 10 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	16-37	22
β-strand	40-46	7	1
α-helix	53-62	10
β-strand	208-214	7	1
β-strand	217-223	7	1
α-helix	234-238	5
β-strand	243-249	7	1
α-helix	266-278	13
β-strand	287-292	6	1
α-helix	294-303	10
α-helix	308-310	3
α-helix	313-317	5
α-helix	326-327	2
α-helix	332-351	20
β-strand	359-363	5	1
α-helix	371-390	20

Chain B: 2 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	30-33	4
β-strand	47-51	5	2
β-strand	58-63	6	3
β-strand	69-74	6	3
β-strand	78-83	6	3
β-strand	88-94	7	3
β-strand	100-105	6	4
β-strand	111-116	6	4
β-strand	120-125	6	4
β-strand	134-140	7	4
β-strand	146-153	8	5
β-strand	156-161	6	5
β-strand	165-170	6	5
β-strand	176-181	6	5
β-strand	187-192	6	6
β-strand	198-203	6	6
β-strand	207-212	6	6
β-strand	218-223	6	6
β-strand	229-234	6	7
β-strand	240-245	6	7
β-strand	250-254	5	7
β-strand	259-264	6	7
β-strand	273-278	6	8
β-strand	284-289	6	8
β-strand	294-298	5	8
β-strand	304-308	5	8
β-strand	315-320	6	2
β-strand	327-331	5	2
β-strand	336-339	4	2

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	8-23	16
α-helix	30-43	14
α-helix	56-58	3

Chain N: 1 helix, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	10-11	2	10
β-strand	17-25	9	9
β-strand	34-39	6	10
β-strand	45-51	7	10
β-strand	58-60	3	10
β-strand	68-73	6	9
β-strand	78-84	7	9
α-helix	88-90	3
β-strand	92-97	6	10
β-strand	118	1	10
β-strand	122-125	4	10

Chain R: 16 helices, 0 β-strands

Element	Residues	Length
α-helix	137-167	31
α-helix	175-195	21
α-helix	196-200	5
α-helix	201-206	6
α-helix	220-222	3
α-helix	225-256	32
α-helix	262-270	9
α-helix	271-275	5
α-helix	276-291	16
α-helix	295-297	3
α-helix	304-335	32
α-helix	344-360	17
α-helix	363-367	5
α-helix	379-399	21
α-helix	400-404	5
α-helix	407-423	17

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	A	protein	394	Homo sapiens	P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	371	Rattus norvegicus	P54311 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Bos taurus	P63212 (AlphaFold model)
Nanobody-35	N	protein	128	synthetic construct
Glucagon-like peptide 1 receptor	R	protein	440	Homo sapiens	P43220 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>8WG7_1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKNTIVKQM
RILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELA
NPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLD
KIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFND
VTAIIFVVASSSYNMVIREDNQTNRLQAALKLFDSIWNNKWLRDTSVILFLNKQDLLAEK
VLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCY
PHFTCAVDTENIRRVFNDCRDIIQRMHLRQYELL

Sequence of entity 2 (B), FASTA

>8WG7_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWNGSSGGGGSGGGGSSG
VSGWRLFKKIS

Sequence of entity 3 (G), FASTA

>8WG7_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (N), FASTA

>8WG7_4 Nanobody-35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSS

Sequence of entity 5 (R), FASTA

>8WG7_5 Glucagon-like peptide 1 receptor (chains R)
RPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDLFCNRTFDEYACWPDGEPGSFVNV
SCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPWRDLSECEESKRGERSSPEEQLLF
LYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKW
MYSTAAQQHQWDGLLSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVLSEQ
WIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGCWTRNSNMNYWLIIRLPILFAIGVNFLI
FVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLRFIK
LFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWERWRLEHLHIQRDSSMKPLKCPTSSL
SSGATAGSSMYTATCQASCS

Primary citation

Molecular features of the ligand-free GLP-1R, GCGR and GIPR in complex with G s proteins. Cong, Z., Zhao, F., Li, Y. et al. Cell Discov (2024) 10:18-18. DOI 10.1038/s41421-024-00649-0 · PubMed

Other PDB entries of the same protein (UniProt P63092 (AlphaFold model), which also has an AlphaFold model), best resolution first:

7BPH 1.57 Å, Crystal structure of GppNHp-bound GNAS in complex with the cyclic peptide inhibitor GN13
6AU6 1.7 Å, Crystal structure of GDP-bound human GNAS R201C mutant
8F0K 1.9 Å, Human Amylin3 Receptor in complex with Gs and Pramlintide analogue peptide San385
7E5E 1.95 Å, Crystal structure of GDP-bound GNAS in complex with the cyclic peptide inhibitor GD20
7MBX 1.95 Å, Human Cholecystokinin 1 receptor (CCK1R) Gs complex
8F0J 2.0 Å, Calcitonin Receptor in complex with Gs and Pramlintide analogue peptide San45
8F2B 2.0 Å, Amylin 3 Receptor in complex with Gs and Pramlintide analogue peptide San45
9XXT 2.0 Å, Cryo-EM structure of lysophosphatidylserine (18:0)-bound GPR174-Gs complex
6X18 2.1 Å, GLP-1 peptide hormone bound to Glucagon-Like peptide-1 (GLP-1) Receptor
6X19 2.1 Å, Non peptide agonist CHU-128, bound to Glucagon-Like peptide-1 (GLP-1) Receptor
9NTU 2.1 Å, Cryo-EM structure of BETP-GLP-1(9-36)-GLP-1R-Gs complex
7RTB 2.14 Å, Peptide-19 bound to the Glucagon-Like Peptide-1 Receptor (GLP-1R)

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