7EVM: Compound 2-bound human GLP-1 receptor-Gs complex

Cryo-EM structure of the compound 2-bound human GLP-1 receptor-Gs complex. Determined by electron microscopy at 2.5 Å resolution. Released 11 Aug 2021.

Method: Electron microscopy
Resolution: 2.5 Å
Organisms: Homo sapiens, Rattus norvegicus, Bos taurus
Chains: 5
Atoms: 8,462
Mol. weight: 160.12 kDa
Ligands: HNO, CLR
Released: 11 Aug 2021

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

Secondary structure: helices and β-sheets

7EVM contains 31 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: 9 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	13-37	25
β-strand	41-47	7	1
α-helix	53-61	9
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	265-277	13
β-strand	286-292	7	1
α-helix	296-303	8
α-helix	313-315	3
α-helix	326-327	2
α-helix	332-350	19
β-strand	359-363	5	1
α-helix	371-388	18

Chain B: 3 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	30-33	4
α-helix	34-36	3
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	121-125	5	4
β-strand	134-139	6	4
β-strand	146-151	6	5
β-strand	156-161	6	5
β-strand	165-170	6	5
β-strand	175-181	7	5
β-strand	187-192	6	6
β-strand	198-203	6	6
β-strand	208-212	5	6
β-strand	218-222	5	6
β-strand	229-234	6	7
β-strand	240-245	6	7
β-strand	249-254	6	7
β-strand	260-265	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: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	8-23	16
α-helix	30-43	14
α-helix	54-55	2
α-helix	56-58	3

Chain N: 3 helices, 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
α-helix	29-31	3
β-strand	34-40	7	10
β-strand	44-51	8	10
β-strand	58	1	10
α-helix	62-64	3
β-strand	68-73	6	9
β-strand	78-84	7	9
α-helix	88-90	3
β-strand	92-98	7	10
β-strand	118	1	10
β-strand	122-125	4	10

Chain R: 12 helices, 0 β-strands

Element	Residues	Length
α-helix	137-142	6
α-helix	145-168	24
α-helix	175-210	36
α-helix	218-221	4
α-helix	227-256	30
α-helix	264-291	28
α-helix	303-336	34
α-helix	346-360	15
α-helix	364-367	4
α-helix	377-399	23
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	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	synthetic construct
Glucagon-like peptide 1 receptor	R	protein	440	Homo sapiens	P43220 (AlphaFold model)

Sequence of entity 1 (A), FASTA

>7EVM_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

>7EVM_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

>7EVM_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
ASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPF
REKKFFCAIL

Sequence of entity 4 (N), FASTA

>7EVM_4 Nanobody-35 (chains N)
MAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASI
SYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYR
GQGTQVTVSSHHHHHHEPEA

Sequence of entity 5 (R), FASTA

>7EVM_5 Glucagon-like peptide 1 receptor (chains R)
RPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDLFCNRTFDEYACWPDGEPGSFVNV
SCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPWRDLSECEESKRGERSSPEEQLLF
LYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKW
MYSTAAQQHQWDGLLSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVLSEQ
WIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGCWTRNSNMNYWLIIRLPILFAIGVNFLI
FVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLRFIK
LFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWERWRLEHLHIQRDSSMKPLKCPTSSL
SSGATAGSSMYTATCQASCS

Ligands and cofactors

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

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 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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