8ITM: GIPR splice variant 2

Cryo-EM structure of GIPR splice variant 2 (SV2) in complex with Gs protein. Determined by electron microscopy at 3.13 Å resolution. Released 18 Oct 2023.

Method: Electron microscopy
Resolution: 3.13 Å
Organisms: Homo sapiens, Bos taurus, Rattus norvegicus
Chains: 5
Atoms: 7,905
Mol. weight: 149.06 kDa
Released: 18 Oct 2023

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

Secondary structure: helices and β-sheets

8ITM contains 27 α-helices and 46 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, 7 β-strands

Element	Residues	Length	Sheet
α-helix	10-39	30
β-strand	41-47	7	1
α-helix	53-59	7
β-strand	208-209	2	1
β-strand	212-214	3	1
β-strand	217-223	7	1
α-helix	235-238	4
β-strand	243-249	7	1
α-helix	265-278	14
β-strand	286-292	7	1
α-helix	294-302	9
α-helix	308-311	4
α-helix	313-315	3
α-helix	332-351	20
β-strand	359-362	4	1
α-helix	371-390	20

Chain B: 4 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	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	121-125	5	4
β-strand	134-139	6	4
β-strand	146-151	6	5
β-strand	157-161	5	5
β-strand	165-168	4	5
β-strand	178-181	4	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
α-helix	272	1
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	317-320	4	2
β-strand	327-330	4	2
β-strand	336-341	6	2

Chain G: 3 helices, 0 β-strands

Element	Residues	Length
α-helix	7-23	17
α-helix	30-43	14
α-helix	54-55	2

Chain N: 2 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	5-6	2	9
β-strand	10-12	3	10
β-strand	17-23	7	9
α-helix	29-31	3
β-strand	34-39	6	10
β-strand	45-47	3	10
β-strand	49	1	11
β-strand	60	1	11
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	123-126	4	10

Chain R: 9 helices, 0 β-strands

Element	Residues	Length
α-helix	64-100	37
α-helix	107-132	26
α-helix	150-185	36
α-helix	195-219	25
α-helix	232-267	36
α-helix	271-289	19
α-helix	291-295	5
α-helix	307-330	24
α-helix	336-353	18

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Gastric inhibitory polypeptide receptor	R	protein	360	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	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	128	synthetic construct

Sequence of entity 1 (R), FASTA

>8ITM_1 Gastric inhibitory polypeptide receptor (chains R)
MNSAHCNFRLPGSSDSPASASREAGITEAGITVAAGFVLRQCGSDGQWGLWRDHTQCENP
EKNEAFLDQRLILERLQVMYTVGYSLSLATLLLALLILSLFRRLHCTRNYIHINLFTSFM
LRAAAILSRDRLLPRPGPYLGDQALALWNQALAACRTAQIVTQYCVGANYTWLLVEGVYL
HSLLVLVGGSEEGHFRYYLLLGWGAPALFVIPWVIVRYLYENTQCWERNEVKAIWWIIRT
PILMTILINFLIFIRILGILLSKLRTRQMRCRDYRLRLARSTLFLVPLLGVHEVVFAPVT
EEQARGALRFAKLGFEIFLSSFQGFLVSVLYCFINKEVQSEIRRGWHHCRLRRSLGEEQR

Sequence of entity 2 (A), FASTA

>8ITM_2 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short (chains A)
MGCLGNSKTEDQRNEEKAQREANKKIEKQLQKDKQVYRATHRLLLLGAGESGKNTIVKQM
RILHVNGFNGEGGEEDPQAARSNSDGEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELA
NPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLD
KIDVIKQDDYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFND
VTAIIFVVASSSYNMVIREDNQTNRLQAALKLFDSIWNNKWLRDTSVILFLNKQDLLAEK
VLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCY
PHFTCAVDTENIRRVFNDCRDIIQRMHLRQYELL

Sequence of entity 3 (B), FASTA

>8ITM_3 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 4 (G), FASTA

>8ITM_4 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREKKFFCAIL

Sequence of entity 5 (N), FASTA

>8ITM_5 Nanobody-35 (chains N)
QVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISY
TGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQ
GTQVTVSS

Primary citation

Molecular basis of signal transduction mediated by the human GIPR splice variants. Zhao, F., Hang, K., Zhou, Q. et al. Proc Natl Acad Sci U S A (2023) 120:e2306145120-e2306145120. DOI 10.1073/pnas.2306145120 · 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…
8WA3 2.86 Å, Cryo-EM structure of peptide free and Gs-coupled GIPR
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…
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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