7VAB: PDB entry 7VAB

Cryo-EM structure of the non-acylated tirzepatide (LY3298176)-bound human GIPR-Gs complex. Determined by electron microscopy at 3.2 Å resolution. Released 2 Mar 2022.

Method: Electron microscopy
Resolution: 3.2 Å
Organisms: Homo sapiens, synthetic construct, Rattus norvegicus
Chains: 6
Atoms: 8,772
Mol. weight: 175.83 kDa
Ligands: CLR
Released: 2 Mar 2022

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

Secondary structure: helices and β-sheets

7VAB contains 29 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	6-32	27
β-strand	34-40	7	1
α-helix	46-53	8
β-strand	184-191	8	1
β-strand	194-201	8	1
α-helix	212-217	6
β-strand	220-226	7	1
α-helix	233-244	12
β-strand	253-259	7	1
α-helix	261-270	10
α-helix	275-278	4
α-helix	280-282	3
α-helix	299-319	21
β-strand	326-330	5	1
α-helix	338-357	20

Chain B: 2 helices, 29 β-strands

Element	Residues	Length	Sheet
α-helix	5-24	20
α-helix	30-33	4
β-strand	43	1	2
β-strand	45-51	7	3
β-strand	58-63	6	4
β-strand	69-74	6	4
β-strand	78-83	6	4
β-strand	89-94	6	4
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	156-161	6	6
β-strand	165-170	6	6
β-strand	176-181	6	6
β-strand	189-192	4	7
β-strand	198-202	5	7
β-strand	208-212	5	7
β-strand	218-222	5	7
β-strand	229-234	6	8
β-strand	240-245	6	8
β-strand	249-254	6	8
β-strand	260-265	6	8
β-strand	273-278	6	2
β-strand	284-289	6	2
β-strand	294-298	5	2
β-strand	304-308	5	2
β-strand	315-320	6	3
β-strand	327-331	5	3
β-strand	336-341	6	3

Chain G: 4 helices, 0 β-strands

Element	Residues	Length
α-helix	7-23	17
α-helix	30-43	14
α-helix	45-47	3
α-helix	53-55	3

Chain N: 1 helix, 11 β-strands

Element	Residues	Length	Sheet
β-strand	3-7	5	9
β-strand	10-12	3	10
β-strand	17-25	9	9
β-strand	34-39	6	10
β-strand	45-51	7	10
β-strand	58-60	3	10
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	122-126	5	10

Chain P: 1 helix, 0 β-strands

Element	Residues	Length	Sheet
α-helix	2-26	25

Chain R: 12 helices, 0 β-strands

Element	Residues	Length
α-helix	32-47	16
α-helix	128-161	34
α-helix	163-165	3
α-helix	168-192	25
α-helix	209-245	37
α-helix	256-280	25
α-helix	297-327	31
α-helix	335-350	16
α-helix	369-382	14
α-helix	384-389	6
α-helix	390-394	5
α-helix	397-410	14

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Gastric inhibitory polypeptide receptor,Gastric inhibitory polypeptide receptor,Gastric inhibitory…	R	protein	573	Homo sapiens	P48546 (AlphaFold model)
Non-acylated_tirzepatide	P	protein	39	synthetic construct
mini-Gs	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	64	Bos taurus	P63212
Nonobody-35	N	protein	140	synthetic construct

Sequence of entity 1 (R), FASTA

>7VAB_1 Gastric inhibitory polypeptide receptor,Gastric inhibitory polypeptide receptor,Gastric inhibitory polypeptide receptor,human glucose-dependent insulinotropic polypeptide receptor (chains R)
RAETGSKGQTAGELYQRWERYRRECQETLAAAEPPSGLACNGSFDMYVCWDYAAPNATAR
ASCPWYLPWHHHVAAGFVLRQCGSDGQWGLWRDHTQCENPEKNEAFLDQRLILERLQVMY
TVGYSLSLATLLLALLILSLFRRLHCTRNYIHINLFTSFMLRAAAILSRDRLLPRPGPYL
GDQALALWNQALAACRTAQIVTQYCVGANYTWLLVEGVYLHSLLVLVGGSEEGHFRYYLL
LGWGAPALFVIPWVIVRYLYENTQCWERNEVKAIWWIIRTPILMTILINFLIFIRILGIL
LSKLRTRQMRCRDYRLRLARSTLFLVPLLGVHEVVFAPVTEEQARGALRFAKLGFEIFLS
SFQGFLVSVLYCFINKEVQSEIRRGWHHCRLRRSLGEEQRGSSGGGGSGGGGSSGVFTLE
DFVGDWEQTAAYNLDQVLEQGGVSSLLQNLAVSVTPIQRIVRSGENALKIDIHVIIPYEG
LSADQMAQIEEVFKVVYPVDDHHFKVILPYGTLVIDGVTPNMLNYFGRPYEGIAVFDGKK
ITVTGTLWNGNKIIDERLITPDGSMLFRVTINS

Sequence of entity 2 (P), FASTA

>7VAB_2 Non-acylated_tirzepatide (chains P)
YAEGTFTSDYSIALDKIAQKAFVQWLIAGGPSSGAPPPS

Sequence of entity 3 (A), FASTA

>7VAB_3 mini-Gs (chains A)
MGCTLSAEDKAAVERSKMIEKQLQKDKQVYRATHRLLLLGADNSGKSTIVKQMRIYHVNG
YSEEECKQYKAVVYSNTIQSIIAIIRAMGRLKIDFGDSARADDARQLFVLAGAAEEGFMT
AELAGVIKRLWKDSGVQACFNRSREYQLNDSAAYYLNDLDRIAQPNYIPTQQDVLRTRVK
TSGIFETKFQVDKVNFHMFDVGAQRDERRKWIQCFNDVTAIIFVVDSSDYNRLQEALNDF
KSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPR
VTRAKYFIRDEFLRISTASGDGRHYCYPHFTCSVDTENARRIFNDCRDIIQRMHLRQYEL
L

Sequence of entity 4 (B), FASTA

>7VAB_4 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 5 (G), FASTA

>7VAB_5 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 (chains G)
MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENP
FREK

Sequence of entity 6 (N), FASTA

>7VAB_6 Nonobody-35 (chains N)
MAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASI
SYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYR
GQGTQVTVSSHHHHHHEPEA

Ligands and cofactors

ID	Name	Formula	Copies
CLR	Cholesterol	C27 H46 O	6

Primary citation

Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors. Zhao, F., Zhou, Q., Cong, Z. et al. Nat Commun (2022) 13:1057-1057. DOI 10.1038/s41467-022-28683-0 · 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…
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…
8ITM 3.13 Å, Cryo-EM structure of GIPR splice variant 2 (SV2) in complex with Gs protein
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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