7fiy

Cryo-EM structure of the tirzepatide-bound human GIPR-Gs complex

Method: ELECTRON MICROSCOPY Dmax: 153.5 Å Quality: REASONABLE

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

;Gastric inhibitory polypeptide receptor,Gastric inhibitory polypeptide receptor,human glucose-dependent insulinotropic polypeptide receptor ;

Homo sapiens

UniProt P48546

State in the Current Structure

Assembly Oligomeric State Construct Mutations and Modifications Ligands, Ions and Associated Components Method and Experimental Conditions Structure Quality
1 Protein heterocomplex Heteromer Protein × 6 PDB declaration: hexameric(6) Consistent with protein copy count Chain R; UniProt 22–421 Mutation:T345F Tiezepatide × 1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 (P04896) Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 (P54311) Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 (P63212) Nanobody-35 × 1 CLR CHOLESTEROL × 6 ELECTRON MICROSCOPY cryo-EM buffer:pH 7.4 cryo-EM vitrification conditions:Cryogen ETHANE Resolution 3.40 Å

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

11 other PDB entries and 13 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name GIPR_HUMAN
Isoform
PDB entities 1
Chains and sequence ranges Author chain R; PDBConstruct 1–400; UniProt 22–421

Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

Bos taurus

UniProt P04896

State in the Current Structure

Assembly Oligomeric State Construct Mutations and Modifications Ligands, Ions and Associated Components Method and Experimental Conditions Structure Quality
1 Protein heterocomplex Heteromer Protein × 6 PDB declaration: hexameric(6) Consistent with protein copy count Chain A; UniProt 1–394 Not recorded ;Gastric inhibitory polypeptide receptor,Gastric inhibitory polypeptide receptor,human glucose-dependent insulinotropic polypeptide receptor ; × 1 (P48546) Tiezepatide × 1 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 (P54311) Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 (P63212) Nanobody-35 × 1 CLR CHOLESTEROL × 6 ELECTRON MICROSCOPY cryo-EM buffer:pH 7.4 cryo-EM vitrification conditions:Cryogen ETHANE Resolution 3.40 Å

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

41 other PDB entries and 42 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name GNAS2_BOVIN
Isoform
PDB entities 3
Chains and sequence ranges Author chain A; PDBConstruct 1–394; UniProt 1–394

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

Rattus norvegicus

UniProt P54311

State in the Current Structure

Assembly Oligomeric State Construct Mutations and Modifications Ligands, Ions and Associated Components Method and Experimental Conditions Structure Quality
1 Protein heterocomplex Heteromer Protein × 6 PDB declaration: hexameric(6) Consistent with protein copy count Chain B; UniProt 2–340 Not recorded ;Gastric inhibitory polypeptide receptor,Gastric inhibitory polypeptide receptor,human glucose-dependent insulinotropic polypeptide receptor ; × 1 (P48546) Tiezepatide × 1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 (P04896) Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 (P63212) Nanobody-35 × 1 CLR CHOLESTEROL × 6 ELECTRON MICROSCOPY cryo-EM buffer:pH 7.4 cryo-EM vitrification conditions:Cryogen ETHANE Resolution 3.40 Å

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

161 other PDB entries and 162 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name GBB1_RAT
Isoform
PDB entities 4
Chains and sequence ranges Author chain B; PDBConstruct 7–345; UniProt 2–340

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

Bos taurus

UniProt P63212

State in the Current Structure

Assembly Oligomeric State Construct Mutations and Modifications Ligands, Ions and Associated Components Method and Experimental Conditions Structure Quality
1 Protein heterocomplex Heteromer Protein × 6 PDB declaration: hexameric(6) Consistent with protein copy count Chain G; UniProt 1–71 Not recorded ;Gastric inhibitory polypeptide receptor,Gastric inhibitory polypeptide receptor,human glucose-dependent insulinotropic polypeptide receptor ; × 1 (P48546) Tiezepatide × 1 Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 (P04896) Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 (P54311) Nanobody-35 × 1 CLR CHOLESTEROL × 6 ELECTRON MICROSCOPY cryo-EM buffer:pH 7.4 cryo-EM vitrification conditions:Cryogen ETHANE Resolution 3.40 Å

Other States of the Same Protein in the Database

Each row is a biological assembly of the same UniProt protein in another PDB entry. The “Difference from current entry” column identifies evidence-level differences; no tag means the currently parsed fields agree.

215 other PDB entries and 216 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name GBG2_BOVIN
Isoform
PDB entities 5
Chains and sequence ranges Author chain G; PDBConstruct 1–71; UniProt 1–71

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.

SAXS scattering curve SAXS Profile

SAXS profile for 7fiy

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 7fiy
Download Download

2. Structure Basics 2. Structure Basics

Entry ID entry_id7fiy
Deposition date deposition_date2021-08-01
Structure title titleCryo-EM structure of the tirzepatide-bound human GIPR-Gs complex
Keywords keywords;Cryo-electron microscopy; G protein-coupled receptor; ligand recognition; receptor activation; unimolecular agonist, STRUCTURAL PROTEIN ;; STRUCTURAL PROTEIN
Experimental Method methodELECTRON MICROSCOPY

3. SAXS Parameters (CRYSOL theoretical calculation) 3. SAXS Parameters (CRYSOL)

Radius of gyration Rg (Guinier) rg_guinier41.19
Radius of gyration Rg (electron density) rg_electron41.31
Forward intensity I(0) i0261742000.00
Molecular weight molecular_weight133040.0 kDa
Excluded volume excluded_volume167280 ų
Envelope volume envelope_volume231250 ų
Hydration-shell volume shell_volume50008 ų
Envelope diameter envelope_diameter162.6
Shell Rg shell_rg42.98
Envelope Rg envelope_rg42.23
Shape Rg shape_rg41.32
Total Rg total_rg41.37
Total atoms total_atoms9367
Residues n_residues1150
Spherical-harmonic order n_harmonics20
q range q_range— – 0.5000 −1
Data points n_points101
Shell type shell_typedirectional
Solvent electron density solvent_density0.3340 e/ų
Shell contrast contrast_shell0.0300 e/ų
CRYSOL version crysol_version4.1.3

4. P(r) Distance Distribution (GNOM inversion) 4. P(r) Analysis (GNOM)

Maximum dimension Dmax dmax153.5
Rg (real space) rg_real41.81
Rg uncertainty (real space) rg_real_error1.96
I(0) (real space) i0_real2.6170e+08
I(0) uncertainty (real space) i0_real_error5.3440e+06
Rg (reciprocal space) rg_reciprocal41.20
I(0) (reciprocal space) i0_reciprocal261600000.0000
Solution quality estimate total_estimate0.5295
Solution quality rating solution_quality REASONABLE a REASONABLE solution
P(r) peaks n_peaks2
Primary peak position r_peak_primary36.4
Skewness Skewness skewness0.803
Kurtosis Kurtosis kurtosis0.214
Angular range angular_range— – 0.1900 −1
Current regularization parameter α current_alpha0.0000
Highest regularization parameter α highest_alpha46560000.0000
Real-space data points n_real_points39
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.447; Stabil: 1.000; Sysdev: 0.046; Positv: 1.000; Valcen: 0.707; Smooth: 0.693

5. Crystallography and Experiment 5. Crystallography & Experiment

6. Entities and Polymers Entities & Polymers (7)

7. Fold Classification (SCOP + CATH) 4 domains

CATH v4.4 (4 domains)

Domain ID domain_id7fiyB01
Class class2 — Mainly Beta
Architecture architecture130 — 7 Propeller
Topology topology10 — Methylamine Dehydrogenase; Chain H
Homologous superfamily homologous superfamily10 — YVTN repeat-like/Quinoprotein amine dehydrogenase
Domain ID domain_id7fiyN01
Class class2 — Mainly Beta
Architecture architecture60 — Sandwich
Topology topology40 — Immunoglobulin-like
Homologous superfamily homologous superfamily10 — Immunoglobulins
Domain ID domain_id7fiyR01
Class class4 — Few Secondary Structures
Architecture architecture10 — Irregular
Topology topology1240 — Hormone receptor fold
Homologous superfamily homologous superfamily10 — GPCR, family 2, extracellular hormone receptor domain
Domain ID domain_id7fiyR02
Class class1 — Mainly Alpha
Architecture architecture20 — Up-down Bundle
Topology topology1070 — Rhopdopsin 7-helix transmembrane proteins
Homologous superfamily homologous superfamily10 — Rhodopsin 7-helix transmembrane proteins

8. Citations (1)

9. Files and Curves (10)