8WA3: Peptide free and Gs-coupled GIPR

Cryo-EM structure of peptide free and Gs-coupled GIPR. Determined by electron microscopy at 2.86 Å resolution. Released 6 Mar 2024.

Method: Electron microscopy
Resolution: 2.86 Å
Organisms: Homo sapiens, Bos taurus, Rattus norvegicus
Chains: 5
Atoms: 8,163
Mol. weight: 174.13 kDa
Released: 6 Mar 2024

Explore 8WA3 in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8WA3 contains 25 α-helices and 47 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: 7 helices, 6 β-strands

Element	Residues	Length	Sheet
α-helix	10-39	30
β-strand	41-47	7	1
α-helix	53-59	7
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	294-303	10
α-helix	332-349	18
β-strand	359-360	2	1
α-helix	370-390	21

Chain B: 2 helices, 28 β-strands

Element	Residues	Length	Sheet
α-helix	4-25	22
α-helix	30-34	5
β-strand	45-51	7	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	120-125	6	4
β-strand	134-140	7	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	250-254	5	7
β-strand	259-263	5	7
β-strand	273-278	6	8
β-strand	284-289	6	8
β-strand	294-298	5	8
β-strand	303-307	5	8
β-strand	315-320	6	2
β-strand	327-331	5	2
β-strand	336-341	6	2

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	7-23	17
α-helix	30-43	14
α-helix	53-55	3
α-helix	56-58	3

Chain N: 1 helix, 13 β-strands

Element	Residues	Length	Sheet
β-strand	4-6	3	9
β-strand	11-12	2	10
β-strand	17-24	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
β-strand	65	1	9
β-strand	68-73	6	9
β-strand	78-84	7	9
β-strand	92-98	7	11
β-strand	118	1	11
β-strand	123-124	2	11
β-strand	125-126	2	10

Chain R: 11 helices, 0 β-strands

Element	Residues	Length
α-helix	129-160	32
α-helix	168-193	26
α-helix	211-246	36
α-helix	256-264	9
α-helix	266-280	15
α-helix	293-328	36
α-helix	332-346	15
α-helix	351-356	6
α-helix	368-389	22
α-helix	390-394	5
α-helix	399-414	16

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Gastric inhibitory polypeptide receptor,Fusion protein	R	protein	573	Homo sapiens	P48546 (AlphaFold model)
Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	A	protein	394	Bos taurus	P04896 (AlphaFold model)
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,O-antigen polymerase	B	protein	371	Rattus norvegicus, Leptolinea tardivitalis	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

Sequence of entity 1 (R), FASTA

>8WA3_1 Gastric inhibitory polypeptide receptor,Fusion protein (chains R)
RAETGSKGQTAGELYQRWERYRRECQETLAAAEPPSGLACNGSFDMYVCWDYAAPNATAR
ASCPWYLPWHHHVAAGFVLRQCGSDGQWGLWRDHTQCENPEKNEAFLDQRLILERLQVMY
TVGYSLSLATLLLALLILSLFRRLHCTRNYIHINLFTSFMLRAAAILSRDRLLPRPGPYL
GDQALALWNQALAACRTAQIVTQYCVGANYTWLLVEGVYLHSLLVLVGGSEEGHFRYYLL
LGWGAPALFVIPWVIVRYLYENTQCWERNEVKAIWWIIRTPILMTILINFLIFIRILGIL
LSKLRTRQMRCRDYRLRLARSTLFLVPLLGVHEVVFAPVTEEQARGALRFAKLGFEIFLS
SFQGFLVSVLYCFINKEVQSEIRRGWHHCRLRRSLGEEQRGSSGGGGSGGGGSSGVFTLE
DFVGDWEQTAAYNLDQVLEQGGVSSLLQNLAVSVTPIQRIVRSGENALKIDIHVIIPYEG
LSADQMAQIEEVFKVVYPVDDHHFKVILPYGTLVIDGVTPNMLNYFGRPYEGIAVFDGKK
ITVTGTLWNGNKIIDERLITPDGSMLFRVTINS

Sequence of entity 2 (A), FASTA

>8WA3_2 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKNTIVKQM
RILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELA
NPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLD
KIDVIKQDDYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFND
VTAIIFVVASSSYNMVIREDNQTNRLQAALKLFDSIWNNKWLRDTSVILFLNKQDLLAEK
VLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCY
PHFTCSVDTENIRRVFNDCRDIIQRMHLRQYELL

Sequence of entity 3 (B), FASTA

>8WA3_3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1,O-antigen polymerase (chains B)
MGSLLQSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHL
AKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACG
GLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQ
QTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFF
PNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCN
VWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWNGSSGGGGSGGGGSSG
VSGWRLFKKIS

Sequence of entity 4 (G), FASTA

>8WA3_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (N), FASTA

>8WA3_5 Nanobody-35 (chains N)
MAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASI
SYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYR
GQGTQVTVSSHHHHHHEPEA

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 P48546 (AlphaFold model), which also has an AlphaFold model), best resolution first:

2QKH 1.9 Å, Crystal structure of the extracellular domain of human GIP receptor in complex with the…
6DKJ 1.95 Å, human GIPR ECD and Fab complex
9XN3 2.74 Å, Glucose-dependent insulinotropic polypeptide receptor-Gs complex activated by the small…
7DTY 2.98 Å, Structural basis of ligand selectivity conferred by the human glucose-dependent…
4HJ0 3.0 Å, Crystal structure of the human GIPr ECD in complex with Gipg013 Fab at 3-A resolution
7RBT 3.08 Å, cryo-EM structure of human Gastric inhibitory polypeptide receptor GIPR bound to…
7FIN 3.1 Å, Cryo-EM structure of the GIPR/GLP-1R/GCGR triagonist peptide 20-bound human GIPR-Gs…
8ITM 3.13 Å, Cryo-EM structure of GIPR splice variant 2 (SV2) in complex with Gs protein
7VAB 3.2 Å, Cryo-EM structure of the non-acylated tirzepatide (LY3298176)-bound human GIPR-Gs complex
8ITL 3.23 Å, Cryo-EM structure of GIPR splice variant 1 (SV1) in complex with Gs protein
7RA3 3.24 Å, cryo-EM of human Gastric inhibitory polypeptide receptor GIPR bound to GIP
8YW4 3.26 Å, Cryo-EM structure of the retatrutide-bound human GIPR-Gs complex

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