9J1P: G1:Ox-bound human GLP-1R-Gs complex

Cryo-EM structure of the g1:Ox-bound human GLP-1R-Gs complex. Determined by electron microscopy at 2.99 Å resolution. Released 26 Feb 2025.

Method: Electron microscopy
Resolution: 2.99 Å
Organisms: Homo sapiens, Rattus norvegicus, Bos taurus
Chains: 6
Atoms: 9,385
Mol. weight: 158.84 kDa
Released: 26 Feb 2025

Explore 9J1P in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

9J1P contains 39 α-helices and 53 β-strands across 6 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: 11 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	14-38	25
β-strand	41-47	7	1
α-helix	49-51	3
α-helix	53-63	11
β-strand	207	1	2
β-strand	212	1	1
β-strand	219-223	5	1
β-strand	224	1	2
α-helix	234-239	6
β-strand	243-249	7	1
α-helix	266-278	13
α-helix	280-282	3
β-strand	287-292	6	1
α-helix	294-303	10
α-helix	308-311	4
α-helix	326-327	2
α-helix	332-349	18
β-strand	359-362	4	1
α-helix	371-390	20

Chain B: 5 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	5-25	21
α-helix	30-34	5
α-helix	38-39	2
β-strand	47-51	5	3
β-strand	58-63	6	4
β-strand	69-74	6	4
β-strand	78-83	6	4
β-strand	88-94	7	4
α-helix	95	1
β-strand	100-105	6	5
β-strand	111-116	6	5
β-strand	121-125	5	5
β-strand	134-139	6	5
β-strand	146-151	6	6
β-strand	156-161	6	6
β-strand	165-170	6	6
β-strand	175-181	7	6
β-strand	187-192	6	7
β-strand	198-203	6	7
β-strand	208-212	5	7
β-strand	221-222	2	7
β-strand	229-232	4	8
β-strand	240-245	6	8
β-strand	250-254	5	8
β-strand	259-264	6	8
α-helix	272	1
β-strand	273-278	6	9
β-strand	284-289	6	9
β-strand	295-298	4	9
β-strand	304-307	4	9
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	336-339	4	3

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	14-23	10
α-helix	30-44	15
α-helix	45-47	3

Chain N: 3 helices, 9 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	10
β-strand	18-25	8	10
α-helix	29-31	3
β-strand	34-39	6	11
β-strand	45-51	7	11
β-strand	58-60	3	11
α-helix	62-64	3
β-strand	69-73	5	10
β-strand	78-83	6	10
α-helix	88-90	3
β-strand	93-98	6	11
β-strand	122-123	2	11

Chain P: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	2-27	26
α-helix	29-32	4
α-helix	41-43	3

Chain R: 14 helices, 8 β-strands

Element	Residues	Length	Sheet
α-helix	32-52	21
β-strand	65-66	2	12
β-strand	71-72	2	12
β-strand	84	1	13
β-strand	99	1	13
β-strand	101	1	14
β-strand	112	1	15
β-strand	119	1	15
β-strand	122	1	14
α-helix	136-168	33
α-helix	175-204	30
α-helix	207-215	9
α-helix	220-222	3
α-helix	225-255	31
α-helix	262-275	14
α-helix	278-290	13
α-helix	303-335	33
α-helix	345-359	15
α-helix	365-368	4
α-helix	378-399	22
α-helix	400-404	5
α-helix	407-422	16

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s)…	A	protein	361	Homo sapiens	P63092 (AlphaFold model), P63096 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	345	Rattus norvegicus	P54311 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	70	Bos taurus	P63212 (AlphaFold model)
Nanobody-35	N	protein	140	Lama glama
g1:Ox	P	protein	49	synthetic construct
Glucagon-like peptide 1 receptor	R	protein	440	Homo sapiens	P43220

Sequence of entity 1 (A), FASTA

>9J1P_1 Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas (chains A)
MGCTLSAEDKAAVERSKMIEKQLQKDKQVYRATHRLLLLGADNSGKSTIVKQMRIYHVNG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQEALNDF
KSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPR
VTRAKYFIRDEFLRISTASGDGRHYCYPHFTCSVDTENARRIFNDCRDIIQRMHLRQYEL
L

Sequence of entity 2 (B), FASTA

>9J1P_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (G), FASTA

>9J1P_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
ASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPF
REKKFFCAIL

Sequence of entity 4 (N), FASTA

>9J1P_4 Nanobody-35 (chains N)
MAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASI
SYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYR
GQGTQVTVSSHHHHHHEPEA

Sequence of entity 5 (P), FASTA

>9J1P_5 g1:Ox (chains P)
HAEGTFTSDVSSYLEGQAAKCFIAWLINCPGECVPGSACPDVCTNTCPL

Sequence of entity 6 (R), FASTA

>9J1P_6 Glucagon-like peptide 1 receptor (chains R)
RPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDLFCNRTFDEYACWPDGEPGSFVNV
SCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPWRDLSECEESKRGERSSPEEQLLF
LYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKW
MYSTAAQQHQWDGLLSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVLSEQ
WIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGCWTRNSNMNYWLIIRLPILFAIGVNFLI
FVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLRFIK
LFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWERWRLEHLHIQRDSSMKPLKCPTSSL
SSGATAGSSMYTATCQASCS

Primary citation

Disulfide-Directed Multicyclic Peptides with N-Terminally Extendable alpha-Helices for Recognition and Activation of G Protein-Coupled Receptors. Fan, S., Li, J., Zhuang, J. et al. J Am Chem Soc (2025) 147:4821-4832. DOI 10.1021/jacs.4c12808 · 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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