6WPW: GCGR-Gs signaling complex

GCGR-Gs signaling complex bound to a designed glucagon derivative. Determined by electron microscopy at 3.1 Å resolution. Released 12 Aug 2020.

Method: Electron microscopy
Resolution: 3.1 Å
Organisms: Homo sapiens, Lama glama, synthetic construct
Chains: 6
Atoms: 9,262
Mol. weight: 166.54 kDa
Released: 12 Aug 2020

Explore 6WPW in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6WPW contains 38 α-helices and 54 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 C: 8 helices, 9 β-strands

Element	Residues	Length	Sheet
α-helix	12-38	27
β-strand	40-42	3	1
β-strand	45-47	3	2
β-strand	209-213	5	1
β-strand	218-222	5	1
β-strand	223	1	2
α-helix	234-237	4
β-strand	243-249	7	2
α-helix	265-277	13
α-helix	280-282	3
β-strand	286-292	7	2
α-helix	294-303	10
α-helix	313-315	3
α-helix	332-352	21
β-strand	359	1	2
β-strand	362-363	2	2
α-helix	371-390	20

Chain D: 3 helices, 30 β-strands

Element	Residues	Length	Sheet
α-helix	5-24	20
α-helix	30-34	5
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	91-94	4	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	157-161	5	6
β-strand	165-168	4	6
β-strand	178-181	4	6
β-strand	187-192	6	7
β-strand	198-203	6	7
β-strand	208-212	5	7
β-strand	218-222	5	7
β-strand	229	1	8
β-strand	233-234	2	9
β-strand	240-243	4	9
β-strand	245	1	8
β-strand	250-254	5	9
β-strand	259-264	6	9
β-strand	273-278	6	10
β-strand	284-289	6	10
β-strand	294-298	5	10
β-strand	304-308	5	10
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	6-23	18
α-helix	27-29	3
α-helix	35-43	9

Chain N: 2 helices, 12 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	11
β-strand	11-12	2	12
β-strand	18-25	8	11
α-helix	29-31	3
β-strand	34-39	6	13
β-strand	45-50	6	13
β-strand	60	1	13
α-helix	62-64	3
β-strand	68-73	6	11
β-strand	78-83	6	11
β-strand	92-98	7	13
β-strand	118	1	13
β-strand	122-124	3	13
β-strand	125-126	2	12

Chain P: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	2-28	27

Chain R: 21 helices, 3 β-strands

Element	Residues	Length	Sheet
α-helix	28-47	20
α-helix	50-52	3
β-strand	77-80	4	14
α-helix	81-82	2
β-strand	95-98	4	14
β-strand	117	1	14
α-helix	123-124	2
α-helix	125-165	41
α-helix	167-169	3
α-helix	173-196	24
α-helix	198-201	4
α-helix	209-211	3
α-helix	222-251	30
α-helix	264-272	9
α-helix	276-286	11
α-helix	305-329	25
α-helix	331-334	4
α-helix	345-352	8
α-helix	355-358	4
α-helix	360-365	6
α-helix	376-388	13
α-helix	392-397	6
α-helix	398-402	5
α-helix	405-422	18

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	C	protein	380	Homo sapiens	P63092 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1	D	protein	358	Homo sapiens	P62873 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2	G	protein	71	Homo sapiens	P59768 (AlphaFold model)
Nb35	N	protein	138	Lama glama
Glucagon derivative ZP3780	P	protein	29	synthetic construct
Glucagon receptor	R	protein	496	Homo sapiens	P47871 (AlphaFold model)

Sequence of entity 1 (C), FASTA

>6WPW_1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains C)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQM
RILHVNGFNGDSEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELANPENQFRVDYILSV
MNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSD
QDLLRCRVLTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVASSSYN
MVIREDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPE
FARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRR
VFNDCRDIIQRMHLRQYELL

Sequence of entity 2 (D), FASTA

>6WPW_2 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 (chains D)
MHHHHHHLEVLFQGPGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGR
IQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMT
CAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSG
DTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTF
TGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSG
RLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Sequence of entity 3 (G), FASTA

>6WPW_3 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 4 (N), FASTA

>6WPW_4 Nb35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSSHHHHHHEPEA

Sequence of entity 5 (P), FASTA

>6WPW_5 Glucagon derivative ZP3780 (chains P)
HSQGTFTSDYSKYLDSRRAEDFVKWLEST

Sequence of entity 6 (R), FASTA

>6WPW_6 Glucagon receptor (chains R)
MKTIIALSYIFCLVFADYKDDDDALEVLFQGPSGQVMDFLFEKWKLYGDQCHHNLSLLPP
PTELVCNRTFDKYSCWPDTPANTTANISCPWYLPWHHKVQHRFVFKRCGPDGQWVRGPRG
QPWRDASQCQMDGEEIEVQKEVAKMYSSFQVMYTVGYSLSLGALLLALAILGGLSKLHCT
RNAIHANLFASFVLKASSVLVIDGLLRTRYSQKIGDDLSVSTWLSDGAVAGCRVAAVFMQ
YGIVANYCWLLVEGLYLHNLLGLATLPERSFFSLYLGIGWGAPMLFVVPWAVVKCLFENV
QCWTSNDNMGFWWILRFPVFLAILINFFIFVRIVQLLVAKLRARQMHHTDYKFRLAKSTL
TLIPLLGVHEVVFAFVTDEHAQGTLRSAKLFFDLFLSSFQGLLVAVLYCFLNKEVQSELR
RRWHRWRLGKVLWEERNTSNHRASSSPGHGPPSKELQFGRGGGSQDSSAETPLAGGLPRL
AESPFGSGHHHHHHHH

Primary citation

Structural insights into differences in G protein activation by family A and family B GPCRs. Hilger, D., Kumar, K.K., Hu, H. et al. Science (2020) 369. DOI 10.1126/science.aba3373 · 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)

Browse structure collections

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