8WG8: Peptide free and Gs-coupled GCGR

Cryo-EM structures of peptide free and Gs-coupled GCGR. Determined by electron microscopy at 2.71 Å resolution. Released 6 Mar 2024.

Method: Electron microscopy
Resolution: 2.71 Å
Organisms: Homo sapiens, Rattus norvegicus, Bos taurus
Chains: 6
Atoms: 8,043
Mol. weight: 153.98 kDa
Released: 6 Mar 2024

Explore 8WG8 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8WG8 contains 30 α-helices and 46 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: 9 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	9-32	24
β-strand	34-39	6	1
α-helix	46-49	4
β-strand	186-191	6	1
β-strand	194-200	7	1
α-helix	211-215	5
β-strand	220-226	7	1
α-helix	233-244	12
β-strand	253-259	7	1
α-helix	261-269	9
α-helix	275-277	3
α-helix	280-283	4
α-helix	299-318	20
β-strand	326-330	5	1
α-helix	338-357	20

Chain B: 2 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	5-25	21
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	89-94	6	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	157-161	5	5
β-strand	165-170	6	5
β-strand	175-181	7	5
β-strand	187-192	6	6
β-strand	199-203	5	6
β-strand	207-210	4	6
β-strand	220-223	4	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	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 E: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	9-12	4

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	8-23	16
α-helix	27-29	3
α-helix	30-43	14

Chain N: 3 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	3-6	4	9
β-strand	12	1	10
β-strand	18-25	8	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	68-73	6	9
β-strand	78-83	6	9
α-helix	88-90	3
β-strand	92-97	6	11
β-strand	118	1	11
β-strand	122-124	3	11
β-strand	126	1	10

Chain R: 12 helices, 0 β-strands

Element	Residues	Length
α-helix	136-164	29
α-helix	172-201	30
α-helix	221-252	32
α-helix	264-271	8
α-helix	274-289	16
α-helix	305-335	31
α-helix	344-354	11
α-helix	363-366	4
α-helix	376-381	6
α-helix	385-397	13
α-helix	398-402	5
α-helix	405-418	14

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	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	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	140	synthetic construct
Glucagon receptor	R	protein	407	Homo sapiens	P47871
Pro-pro-pro-pro-phe-ser-asn-leu-val-met-asp-asp-leu-lys-asn-lys-lys	E	protein	17	Spodoptera frugiperda

Sequence of entity 1 (A), FASTA

>8WG8_1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCTLSAEDKAAVERSKMIEKQLQKDKQVYRATHRLLLLGADNSGKSTIVKQMRIYHVNG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVASSSYNRLQEALNDF
KSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPR
VTRAKYFIRDEFLRISTASGDGRHYCYPHFTCSVDTENARRVFNDCRDIIQRMHLRQYEL
L

Sequence of entity 2 (B), FASTA

>8WG8_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

>8WG8_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (N), FASTA

>8WG8_4 Nanobody-35 (chains N)
MAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASI
SYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYR
GQGTQVTVSSHHHHHHEPEA

Sequence of entity 5 (R), FASTA

>8WG8_5 Glucagon receptor (chains R)
AQVMDFLFEKWKLYGDQCHHNLSLLPPPTELVCNRTFDKYSCWPDTPANTTANISCPWYL
PWHHKVQHRFVFKRCGPDGQWVRGPRGQPWRDASQCQMDGEEIEVQKEVAKMYSSFQVMY
TVGYSLSLGALLLALAILGGLSKLHCTRNAIHANLFASFVLKASSVLVIDGLLRTRYSQK
IGDDLSVSTWLSDGAVAGCRVAAVFMQYGIVANYCWLLVEGLYLHNLLGLATLPERSFFS
LYLGIGWGAPMLFVVPWAVVKCLFENVQCWTSNDNMGFWWILRFPVFLAILINFFIFVRI
VQLLVAKLRARQMHHTDYKFRLAKSTLTLIPLLGVHEVVFAFVTDEHAQGTLRSAKLFFD
LFLSSFQGLLVAVLYCFLNKEVQSELRRRWHRWRLGKVLWEERNTSN

Sequence of entity 6 (E), FASTA

>8WG8_6 PRO-PRO-PRO-PRO-PHE-SER-ASN-LEU-VAL-MET-ASP-ASP-LEU-LYS-ASN-LYS-LYS (chains E)
PPPPFSNLVMDDLKNKK

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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