8JIS: PDB entry 8JIS

Cryo-EM structure of the GLP-1R/GCGR dual agonist peptide15-bound human GLP-1R-Gs complex. Determined by electron microscopy at 2.46 Å resolution. Released 8 Nov 2023.

Method: Electron microscopy
Resolution: 2.46 Å
Organisms: Homo sapiens, Rattus norvegicus, synthetic construct
Chains: 6
Atoms: 9,158
Mol. weight: 148.09 kDa
Released: 8 Nov 2023

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

Secondary structure: helices and β-sheets

8JIS contains 36 α-helices and 48 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: 8 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	8-31	24
β-strand	33-40	8	1
α-helix	46-52	7
β-strand	184-191	8	1
β-strand	194-201	8	1
α-helix	211-215	5
β-strand	220-226	7	1
α-helix	230-232	3
α-helix	233-245	13
β-strand	254-259	6	1
α-helix	264-267	4
α-helix	299-319	21
β-strand	326-329	4	1
α-helix	339-357	19

Chain B: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-23	20
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
α-helix	95	1
β-strand	100-105	6	4
β-strand	111-116	6	4
β-strand	121-125	5	4
β-strand	135-139	5	4
β-strand	146-151	6	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	229-232	4	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	295-298	4	8
β-strand	303-307	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	7-22	16
α-helix	30-43	14
α-helix	53-55	3

Chain N: 2 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	11	1	10
β-strand	17-25	9	9
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	9
β-strand	78-84	7	9
β-strand	92-98	7	11
β-strand	118	1	11
β-strand	122-124	3	11
β-strand	125	1	10

Chain P: 2 helices, 0 β-strands

Element	Residues	Length	Sheet
α-helix	2-23	22
α-helix	24-28	5

Chain R: 18 helices, 2 β-strands

Element	Residues	Length	Sheet
α-helix	32-48	17
α-helix	54-57	4
α-helix	71-73	3
α-helix	84-86	3
α-helix	90-92	3
β-strand	112-114	3	12
β-strand	118-119	2	12
α-helix	140-168	29
α-helix	175-204	30
α-helix	206-210	5
α-helix	217-220	4
α-helix	224-255	32
α-helix	262-291	30
α-helix	303-336	34
α-helix	344-353	10
α-helix	357-360	4
α-helix	363-366	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(s) subunit alpha isoforms short	A	protein	356	Homo sapiens	P63092 (AlphaFold model), P63096 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	B	protein	338	Rattus norvegicus	P54311 (AlphaFold model)
Peptide 15	P	protein	29	synthetic construct
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	57	Bos taurus	P63212 (AlphaFold model)
Nanobody 35	N	protein	126	Escherichia coli
Glucagon-like peptide 1 receptor	R	protein	394	Homo sapiens	P43220

Sequence of entity 1 (A), FASTA

>8JIS_1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
SAEDKAAVERSKMIEKQLQKDKQVYRATHRLLLLGADNSGKSTIVKQMRIYHVNGYSEEE
CKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMTAELAG
VIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVKTSGIF
ETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQEALNDFKSIWN
NRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAK
YFIRDEFLRISTASGDGRHYCYPHFTCSVDTENIRRVFNDCRDIIQRMHLRQYELL

Sequence of entity 2 (B), FASTA

>8JIS_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
ELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYAMH
WGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNICS
IYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTFTG
HTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNAFA
TGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDALKA
DRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (P), FASTA

>8JIS_3 Peptide 15 (chains P)
HSQGTFTSDYSKYLDEQAAKEFIAWLMNT

Sequence of entity 4 (G), FASTA

>8JIS_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
TASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPFR

Sequence of entity 5 (N), FASTA

>8JIS_5 Nanobody 35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTV

Sequence of entity 6 (R), FASTA

>8JIS_6 Glucagon-like peptide 1 receptor (chains R)
VSLWETVQKWREYRRQCQRSLTEDPPPATDLFCNRTFDEYACWPDGEPGSFVNVSCPWYL
PWASSVPQGHVYRFCTAEGLWLQKDNSSLPWRDLSECEESKRGERSSPEEQLLFLYIIYT
VGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKWMYSTAA
QQHQWDGLLSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVLSEQWIFRLY
VSIGWGVPLLFVVPWGIVKYLYEDEGCWTRNSNMNYWLIIRLPILFAIGVNFLIFVRVIC
IVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLRFIKLFTELS
FTSFQGLMVAILYCFVNNEVQLEFRKSWERWRLE

Primary citation

Structural analysis of the dual agonism at GLP-1R and GCGR. Li, Y., Zhou, Q., Dai, A. et al. Proc Natl Acad Sci U S A (2023) 120:e2303696120-e2303696120. DOI 10.1073/pnas.2303696120 · 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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