7DUQ: Glucagon-like peptide 1

Cryo-EM structure of the compound 2 and GLP-1-bound human GLP-1 receptor-Gs complex. Determined by electron microscopy at 2.5 Å resolution. Released 14 Jul 2021.

Method: Electron microscopy
Resolution: 2.5 Å
Organisms: Homo sapiens, Rattus norvegicus, Bos taurus
Chains: 6
Atoms: 9,602
Mol. weight: 163.81 kDa
Ligands: CLR, HNO
Released: 14 Jul 2021

Explore 7DUQ in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

7DUQ contains 41 α-helices and 57 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: 10 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	12-38	27
β-strand	40-47	8	6
α-helix	49-51	3
α-helix	53-62	10
β-strand	208-214	7	6
β-strand	217-223	7	6
β-strand	243-248	6	6
α-helix	265-278	14
β-strand	286-291	6	6
α-helix	294-302	9
α-helix	308-311	4
α-helix	313-317	5
α-helix	326-327	2
α-helix	332-350	19
β-strand	359-363	5	6
α-helix	371-390	20

Chain B: 4 helices, 29 β-strands

Element	Residues	Length	Sheet
α-helix	4-23	20
α-helix	30-33	4
α-helix	34-36	3
β-strand	43	1	7
β-strand	47-51	5	8
β-strand	58-63	6	9
β-strand	69-74	6	9
β-strand	78-83	6	9
β-strand	88-94	7	9
β-strand	100-105	6	10
β-strand	111-116	6	10
β-strand	120-125	6	10
β-strand	134-140	7	10
β-strand	146-151	6	11
β-strand	156-161	6	11
β-strand	166-170	5	11
β-strand	176-180	5	11
β-strand	187-192	6	12
β-strand	198-203	6	12
β-strand	207-212	6	12
β-strand	217-222	6	12
β-strand	229-234	6	13
β-strand	240-245	6	13
β-strand	250-254	5	13
β-strand	259-264	6	13
α-helix	272	1
β-strand	273-278	6	7
β-strand	284-289	6	7
β-strand	294-298	5	7
β-strand	303-308	6	7
β-strand	315-320	6	8
β-strand	327-331	5	8
β-strand	336-339	4	8

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	10-23	14
α-helix	30-43	14
α-helix	53-55	3

Chain N: 3 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	14
β-strand	10-11	2	15
β-strand	18-25	8	14
α-helix	29-31	3
β-strand	34-39	6	15
β-strand	45-51	7	15
β-strand	58-60	3	15
α-helix	62-64	3
β-strand	68-73	6	14
β-strand	78-83	6	14
α-helix	88-90	3
β-strand	92-98	7	15
β-strand	118	1	15
β-strand	122-125	4	15

Chain P: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	8-34	27

Chain R: 20 helices, 11 β-strands

Element	Residues	Length	Sheet
α-helix	32-52	21
α-helix	54-55	2
β-strand	62	1	1
β-strand	65-66	2	2
β-strand	71-72	2	2
β-strand	75	1	1
β-strand	80-84	5	3
α-helix	85-86	2
β-strand	99-103	5	3
β-strand	104	1	4
β-strand	110	1	4
α-helix	111	1
β-strand	112	1	5
β-strand	119	1	5
α-helix	120	1
β-strand	121-122	2	3
α-helix	138-168	31
α-helix	170-172	3
α-helix	175-204	30
α-helix	207-214	8
α-helix	224-255	32
α-helix	262-270	9
α-helix	271-275	5
α-helix	278-291	14
α-helix	303-337	35
α-helix	345-360	16
α-helix	362-365	4
α-helix	377-392	16
α-helix	394-399	6
α-helix	400-404	5
α-helix	407-421	15

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Glucagon-like peptide 1	P	protein	30	Homo sapiens	P01275 (AlphaFold model)
Glucagon-like peptide 1 receptor	R	protein	440	Homo sapiens	P43220 (AlphaFold model)
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	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
Nanobody-35	N	protein	140	synthetic construct

Sequence of entity 1 (P), FASTA

>7DUQ_1 Glucagon-like peptide 1 (chains P)
HAEGTFTSDVSSYLEGQAAKEFIAWLVKGR

Sequence of entity 2 (R), FASTA

>7DUQ_2 Glucagon-like peptide 1 receptor (chains R)
RPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDLFCNRTFDEYACWPDGEPGSFVNV
SCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPWRDLSECEESKRGERSSPEEQLLF
LYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKW
MYSTAAQQHQWDGLLSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVLSEQ
WIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGCWTRNSNMNYWLIIRLPILFAIGVNFLI
FVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLRFIK
LFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWERWRLEHLHIQRDSSMKPLKCPTSSL
SSGATAGSSMYTATCQASCS

Sequence of entity 3 (A), FASTA

>7DUQ_3 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKNTIVKQM
RILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELA
NPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLD
KIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFND
VTAIIFVVASSSYNMVIREDNQTNRLQAALKLFDSIWNNKWLRDTSVILFLNKQDLLAEK
VLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCY
PHFTCAVDTENIRRVFNDCRDIIQRMHLRQYELL

Sequence of entity 4 (B), FASTA

>7DUQ_4 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains B)
MGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 5 (G), FASTA

>7DUQ_5 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
ASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPF
REKKFFCAIL

Sequence of entity 6 (N), FASTA

>7DUQ_6 Nanobody-35 (chains N)
MAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASI
SYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYR
GQGTQVTVSSHHHHHHEPEA

Ligands and cofactors

ID	Name	Formula	Copies
CLR	Cholesterol	C27 H46 O	7
HNO	N-tert-butyl-6,7-bis(chloranyl)quinoxalin-2-amine	C12 H13 Cl2 N3	1

Primary citation

Molecular insights into ago-allosteric modulation of the human glucagon-like peptide-1 receptor. Cong, Z., Chen, L.N., Ma, H. et al. Nat Commun (2021) 12:3763-3763. DOI 10.1038/s41467-021-24058-z · PubMed

Other PDB entries of the same protein (UniProt P01275 (AlphaFold model), which also has an AlphaFold model), best resolution first:

6PHI 1.1 Å, Crystal structure of native glucagon in space group I41 at 1.1 A resolution
6PHK 1.18 Å, Crystal structure of glucagon analog with mono-stereoinversion at position 21 (D-Asp21)…
8ANK 1.3 Å, Structure of the amyloid-forming peptide pEFIAWL from human GLP-1
6PHO 1.42 Å, Crystal structure of glucagon analog with selenomethionine substitutions at position 1…
6PHL 1.44 Å, Crystal structure of glucagon analog with mono-stereoinversion at position 23 (D-Val23)…
8ANJ 1.55 Å, Structure of the amyloid-forming peptide DFINWL from human GLP-2
6PHP 1.65 Å, Crystal structure of glucagon analog with 4-bromo-phenylalanine substitutions at…
4ZGM 1.8 Å, Crystal structure of Semaglutide peptide backbone in complex with the GLP-1 receptor…
5OTU 1.8 Å, Extracellular domain of GLP-1 receptor in complex with GLP-1 variant Ala8Hcs/Thr11Hcs
6PHJ 1.99 Å, Crystal structure of native glucagon in space group P213 at 1.99 A resolution
5OTV 2.0 Å, Extracellular domain of GLP-1 receptor in complex with GLP-1 variant Ala8Cyc/Thr11Hcs
5OTX 2.0 Å, Extracellular domain of GLP-1 receptor in complex with GLP-1 variant Ala8Cys/Thr11Cys

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