7rbt

cryo-EM structure of human Gastric inhibitory polypeptide receptor GIPR bound to tirzepatide

Method: ELECTRON MICROSCOPY

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1. Protein Identity and Related Structures Protein Identity & Related Structures

Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

Homo sapiens

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein heterocomplex	Heteromer	Protein 7	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 （P62873） Single-chain variable fragment 16 × 1 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 （P59768） nanobody 35 × 1 Tirzepatide × 1 Gastric inhibitory polypeptide receptor × 1 （P48546） ;2-fluoro-4-[(1R)-6-methoxy-1-methyl-2-{(1S)-1-[4-(propan-2-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinolin-5-yl]-6-[(2-methylpropyl)amino]phenol ; × 1	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	GNAS2-2_HUMAN
Isoform	—
PDB entities	1
Chains and sequence ranges	Author chain A； PDBConstruct 19–373； UniProt 26–380

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

Homo sapiens

UniProt P62873

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein heterocomplex	Heteromer	Protein 7	Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 （P63092-2） Single-chain variable fragment 16 × 1 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 （P59768） nanobody 35 × 1 Tirzepatide × 1 Gastric inhibitory polypeptide receptor × 1 （P48546） ;2-fluoro-4-[(1R)-6-methoxy-1-methyl-2-{(1S)-1-[4-(propan-2-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinolin-5-yl]-6-[(2-methylpropyl)amino]phenol ; × 1	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	GBB1_HUMAN
Isoform	—
PDB entities	2
Chains and sequence ranges	Author chain B； PDBConstruct 12–350； UniProt 2–340

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

Homo sapiens

UniProt P59768

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein heterocomplex	Heteromer	Protein 7	Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 （P63092-2） Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 （P62873） Single-chain variable fragment 16 × 1 nanobody 35 × 1 Tirzepatide × 1 Gastric inhibitory polypeptide receptor × 1 （P48546） ;2-fluoro-4-[(1R)-6-methoxy-1-methyl-2-{(1S)-1-[4-(propan-2-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinolin-5-yl]-6-[(2-methylpropyl)amino]phenol ; × 1	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	GBG2_HUMAN
Isoform	—
PDB entities	4
Chains and sequence ranges	Author chain G； PDBConstruct 1–71； UniProt 1–71

Gastric inhibitory polypeptide receptor

Homo sapiens

UniProt P48546

State in the Current Structure

Assembly	Physical composition	Protein state	Molecular copy count	Associated components	Data consistency
1	Protein heterocomplex	Heteromer	Protein 7	Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 （P63092-2） Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 （P62873） Single-chain variable fragment 16 × 1 Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 （P59768） nanobody 35 × 1 Tirzepatide × 1 ;2-fluoro-4-[(1R)-6-methoxy-1-methyl-2-{(1S)-1-[4-(propan-2-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinolin-5-yl]-6-[(2-methylpropyl)amino]phenol ; × 1	Consistent with protein count

Other States of the Same Protein in the Database

View Construct and Data Evidence

UniProt name	GIPR_HUMAN
Isoform	—
PDB entities	7
Chains and sequence ranges	Author chain R； PDBConstruct 19–463； UniProt 22–466

The page prioritizes protein identity, the current assembly, associated components, oligomeric state and cross-PDB links. Chain mapping and sequence ranges are retained as data evidence. Internal IDs, import timestamps and assembly operation expressions are maintenance fields and are not shown here.

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2. Structure Basics 2. Structure Basics

Entry ID entry_id	7rbt
Deposition date deposition_date	2021-07-06
Structure title title	cryo-EM structure of human Gastric inhibitory polypeptide receptor GIPR bound to tirzepatide
Keywords keywords	Class B GPCR, glucagon-like peptide-1 receptor, G protein nucleotide exchange factor., MEMBRANE PROTEIN; MEMBRANE PROTEIN
Experimental Method method	ELECTRON MICROSCOPY

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3. Official assembly/model SAXS Official SAXS Profiles

This page reads only the latest assembly calculations. Every curve maps to an explicit PDB entry, official biological assembly and coordinate model.

7rbt__assembly_1__model_1

Assembly 1 · Model 1 · CRYSOL 4.1.3-1-20251215 (887e7ef)

Download this curve (.dat)

7rbt__assembly_1__model_1 | I(q)

100 plotted points; both axes use logarithmic scales.

7rbt__assembly_1__model_1 | P(r) · Pending

P(r) will be calculated and displayed separately for the same assembly/model.

Rg（Guinier）	43.83 Å
Rg (electron density)	43.85 Å
Total Rg	43.86 Å
Atom count	10881
Residues	1384
Excluded volume	193260 Å³
Maximum q	0.500 Å⁻¹

Assembly	Model	Structure unit	Oligomeric description	Status	CRYSOL	Actions
1	1	`7rbt__assembly_1__model_1`	heptameric （7）	Success	4.1.3-1-20251215 (887e7ef)	View Download

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4. Crystallography and Experiment 4. Crystallography & Experiment

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5. Entities and Polymers Entities & Polymers (8)

Entity 1 Entity 1 polymer

Description description	Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
Molecular weight formula_weight	43385.2 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	A
Atom count atom_count	10881

MGCTLSAEDKAAVERSKMIEKQLQKDKQVYRATHRLLLLGAGESGKSTIVKQMRILHVNGFNGDSEKATKVQDIKNNLKEAIETIVAAMSNLVPPVELANPENQFRVDYILSVMNVPDFDFPPEFYEHAKALWEDEGVRACYERSNEYQLIDCAQYFLDKIDVIKQADYVPSDQDLLRCRVLTSGIFETKFQVDKVNFHMFDVGGQRDERRKWIQCFNDVTAIIFVVASSSYNMVIREDNQTNRLQEALNLFKSIWNNRWLRTISVILFLNKQDLLAEKVLAGKSKIEDYFPEFARYTTPEDATPEPGEDPRVTRAKYFIRDEFLRISTASGDGRHYCYPHFTCAVDTENIRRVFNDCRDIIQRMHLRQYELL

Source Source

Source organism organism	Homo sapiens
Common name common_name	Human
NCBI taxonomy ID ncbi_taxonomy_id	9606
Host organism host_organism	Trichoplusia ni

Entity 2 Entity 2 polymer

Description description	Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
Molecular weight formula_weight	38534.1 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	B

MHHHHHHGSSGSELDQLRQEAEQLKNQIRDARKACADATLSQITNNIDPVGRIQMRTRRTLRGHLAKIYAMHWGTDSRLLVSASQDGKLIIWDSYTTNKVHAIPLRSSWVMTCAYAPSGNYVACGGLDNICSIYNLKTREGNVRVSRELAGHTGYLSCCRFLDDNQIVTSSGDTTCALWDIETGQQTTTFTGHTGDVMSLSLAPDTRLFVSGACDASAKLWDVREGMCRQTFTGHESDINAICFFPNGNAFATGSDDATCRLFDLRADQELMTYSHDNIICGITSVSFSKSGRLLLAGYDDFNCNVWDALKADRAGVLAGHDNRVSCLGVTDDGMAVATGSWDSFLKIWN

Source Source

Source organism organism	Homo sapiens
Common name common_name	Human
NCBI taxonomy ID ncbi_taxonomy_id	9606
Host organism host_organism	Trichoplusia ni

Entity 3 Entity 3 polymer

Description description	Single-chain variable fragment 16
Molecular weight formula_weight	31870.6 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	E

MLLVNQSHQGFNKEHTSKMVSAIVLYVLLAAAAHSAFADVQLVESGGGLVQPGGSRKLSCSASGFAFSSFGMHWVRQAPEKGLEWVAYISSGSGTIYYADTVKGRFTISRDDPKNTLFLQMTSLRSEDTAMYYCVRSIYYYGSSPFDFWGQGTTLTVSSGGGGSGGGGSGGGGSDIVMTQATSSVPVTPGESVSISCRSSKSLLHSNGNTYLYWFLQRPGQSPQLLIYRMSNLASGVPDRFSGSGSGTAFTLTISRLEAEDVGVYYCMQHLEYPLTFGAGTKLELKAAAHHHHHHHH

Source Source

Source organism organism	Mus musculus
NCBI taxonomy ID ncbi_taxonomy_id	10090
Host organism host_organism	Spodoptera frugiperda

Entity 4 Entity 4 polymer

Description description	Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
Molecular weight formula_weight	7861.1 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	G

MASNNTASIAQARKLVEQLKMEANIDRIKVSKAAADLMAYCEAHAKEDPLLTPVPASENPFREKKFFCAIL

Source Source

Source organism organism	Homo sapiens
Common name common_name	Human
NCBI taxonomy ID ncbi_taxonomy_id	9606
Host organism host_organism	Spodoptera frugiperda

Entity 5 Entity 5 polymer

Description description	nanobody 35
Molecular weight formula_weight	17352.5 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	N

MKYLLPTAAAGLLLLAAQPAMAQVQLQESGGGLVQPGGSLRLSCAASGFTFSNYKMNWVRQAPGKGLEWVSDISQSGASISYTGSVKGRFTISRDNAKNTLYLQMNSLKPEDTAVYYCARCPAPFTRDCFDVTSTTYAYRGQGTQVTVSSHHHHHHEPEA

Source Source

Source organism organism	Lama glama
NCBI taxonomy ID ncbi_taxonomy_id	9844
Host organism host_organism	Escherichia coli

Entity 6 Entity 6 polymer

Description description	Tirzepatide
Molecular weight formula_weight	4072.5 kDa
Source method src_method	syn
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	P

YAEGTFTSDYSIALDKIAQKAFVQWLIAGGPSSGAPPPS

Entity 7 Entity 7 polymer

Description description	Gastric inhibitory polypeptide receptor
Molecular weight formula_weight	52871.8 kDa
Source method src_method	man
Copy count entity_count	1

Polymer Polymer

Polymer type type	polypeptide(L)
Chain IDs strand_id	R

DYKDDDDAAALEVLFQGPRAETGSKGQTAGELYQRWERYRRECQETLAAAEPPSGLACNGSFDMYVCWDYAAPNATARASCPWYLPWHHHVAAGFVLRQCGSDGQWGLWRDHTQCENPEKNEAFLDQRLILERLQVMYTVGYSLSLATLLLALLILSLFRRLHCTRNYIHINLFTSFMLRAAAILSRDRLLPRPGPYLGDQALALWNQALAACRTAQIVTQYCVGANYTWLLVEGVYLHSLLVLVGGSEEGHFRYYLLLGWGAPALFVIPWVIVRYLYENTQCWERNEVKAIWWIIRTPILMTILINFLIFIRILGILLSKLRTRQMRCRDYRLRLARSTLTLVPLLGVHEVVFAPVTEEQARGALRFAKLGFEIFLSSFQGFLVSVLYCFINKEVQSEIRRGWHHCRLRRSLGEEQRQLPERAFRALPSGSGPGEVPTSRGLSSGTLPGPGNEASRELESYC

Source Source

Source organism organism	Homo sapiens
Common name common_name	Human
NCBI taxonomy ID ncbi_taxonomy_id	9606
Host organism host_organism	Spodoptera frugiperda

Entity 8 Entity 8 non-polymer

Description description	;2-fluoro-4-[(1R)-6-methoxy-1-methyl-2-{(1S)-1-[4-(propan-2-yl)phenyl]ethyl}-1,2,3,4-tetrahydroisoquinolin-5-yl]-6-[(2-methylpropyl)amino]phenol ;
Molecular weight formula_weight	504.7 kDa
Source method src_method	syn
Copy count entity_count	1

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6. Fold Classification (SCOP + CATH) 2 domains

CATH v4.4 (2 domains)

Domain ID domain_id	7rbtB01
Class class	2 — Mainly Beta
Architecture architecture	130 — 7 Propeller
Topology topology	10 — Methylamine Dehydrogenase; Chain H
Homologous superfamily homologous superfamily	10 — YVTN repeat-like/Quinoprotein amine dehydrogenase

Domain ID domain_id	7rbtR01
Class class	1 — Mainly Alpha
Architecture architecture	20 — Up-down Bundle
Topology topology	1070 — Rhopdopsin 7-helix transmembrane proteins
Homologous superfamily homologous superfamily	10 — Rhodopsin 7-helix transmembrane proteins

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Unit-cell length a length_a	1.000 Å
Unit-cell length b length_b	1.000 Å
Unit-cell length c length_c	1.000 Å
Unit-cell angle α angle_alpha	90.00 °
Unit-cell angle β angle_beta	90.00 °
Unit-cell angle γ angle_gamma	90.00 °
Molecules per unit cell Z z_pdb	—

Space group space_group	P 1
Space-group number int_tables_number	1
Crystal system crystal_system	triclinic

Resolution resolution	3.08 Å
Resolution测定Method resolution_method	—
颗粒数 num_particles	259349

cryo-EM structure of human Gastric inhibitory polypeptide receptor GIPR bound to tirzepatide

1. Protein Identity and Related Structures Protein Identity & Related Structures

Isoform Gnas-2 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

State in the Current Structure

Other States of the Same Protein in the Database

Monomer

Homodimer

Homotetramer

Other homooligomers

Heteromeric or nucleic-acid complex

Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1

State in the Current Structure

Other States of the Same Protein in the Database

Monomer

Homodimer

Homotetramer

Other homooligomers

Heteromeric or nucleic-acid complex

Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2

State in the Current Structure

Other States of the Same Protein in the Database

Monomer

Homodimer

Homotetramer

Other homooligomers

Heteromeric or nucleic-acid complex

Gastric inhibitory polypeptide receptor

State in the Current Structure

Other States of the Same Protein in the Database

Monomer

Homodimer

Homotetramer

Other homooligomers

Heteromeric or nucleic-acid complex

2. Structure Basics 2. Structure Basics

3. Official assembly/model SAXS Official SAXS Profiles

7rbt__assembly_1__model_1

7rbt__assembly_1__model_1 | I(q)

7rbt__assembly_1__model_1 | P(r) · Pending

4. Crystallography and Experiment 4. Crystallography & Experiment

Unit cell Unit Cell

Symmetry Symmetry

冷冻电镜 EM 3D

5. Entities and Polymers Entities & Polymers (8)

Entity 1 Entity 1 polymer

Polymer Polymer

Source Source

Entity 2 Entity 2 polymer

Polymer Polymer

Source Source

Entity 3 Entity 3 polymer

Polymer Polymer

Source Source

Entity 4 Entity 4 polymer

Polymer Polymer

Source Source

Entity 5 Entity 5 polymer

Polymer Polymer

Source Source

Entity 6 Entity 6 polymer

Polymer Polymer

Entity 7 Entity 7 polymer

Polymer Polymer

Source Source

Entity 8 Entity 8 non-polymer

6. Fold Classification (SCOP + CATH) 2 domains

CATH v4.4 (2 domains)

7. Citations (1)