7vbi

Cryo-EM structure of the non-acylated tirzepatide (LY3298176)-bound human GLP-1R-Gs complex

Method: ELECTRON MICROSCOPY Dmax: 156.8 Å Quality: REASONABLE

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

Isoform 3 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short

Homo sapiens

UniProt P63092-3

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 12–379 Not recorded Nanobody 35 × 1 Non-acylated_tirzepatide × 1 Glucagon-like peptide 1 receptor × 1 (P43220) 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) ELECTRON MICROSCOPY cryo-EM buffer:pH 7.4 cryo-EM vitrification conditions:Cryogen ETHANE Resolution 3.00 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.

No other PDB entry for the same UniProt protein was found.

View Construct and Data Evidence
UniProt name GNAS2-3_HUMAN
Isoform
PDB entities 1
Chains and sequence ranges Author chain A; PDBConstruct 1–357; UniProt 12–379

Glucagon-like peptide 1 receptor

Homo sapiens

UniProt P43220

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 24–463 Not recorded Isoform 3 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 (P63092-3) Nanobody 35 × 1 Non-acylated_tirzepatide × 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) ELECTRON MICROSCOPY cryo-EM buffer:pH 7.4 cryo-EM vitrification conditions:Cryogen ETHANE Resolution 3.00 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.

69 other PDB entries and 79 assemblies. Open the comparison page and filter oligomeric states

View Construct and Data Evidence
UniProt name GLP1R_HUMAN
Isoform
PDB entities 4
Chains and sequence ranges Author chain R; PDBConstruct 1–440; UniProt 24–463

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 Isoform 3 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 (P63092-3) Nanobody 35 × 1 Non-acylated_tirzepatide × 1 Glucagon-like peptide 1 receptor × 1 (P43220) Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 × 1 (P63212) ELECTRON MICROSCOPY cryo-EM buffer:pH 7.4 cryo-EM vitrification conditions:Cryogen ETHANE Resolution 3.00 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 5
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 2–71 Not recorded Isoform 3 of Guanine nucleotide-binding protein G(s) subunit alpha isoforms short × 1 (P63092-3) Nanobody 35 × 1 Non-acylated_tirzepatide × 1 Glucagon-like peptide 1 receptor × 1 (P43220) Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 × 1 (P54311) ELECTRON MICROSCOPY cryo-EM buffer:pH 7.4 cryo-EM vitrification conditions:Cryogen ETHANE Resolution 3.00 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 6
Chains and sequence ranges Author chain G; PDBConstruct 1–70; UniProt 2–71

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 7vbi

P(r) Distance Distribution P(r) Distribution

P(r) distribution for 7vbi
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2. Structure Basics 2. Structure Basics

Entry ID entry_id7vbi
Deposition date deposition_date2021-08-31
Structure title titleCryo-EM structure of the non-acylated tirzepatide (LY3298176)-bound human GLP-1R-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_guinier42.08
Radius of gyration Rg (electron density) rg_electron42.41
Forward intensity I(0) i0256275000.00
Molecular weight molecular_weight130940.0 kDa
Excluded volume excluded_volume164100 ų
Envelope volume envelope_volume223920 ų
Hydration-shell volume shell_volume48006 ų
Envelope diameter envelope_diameter164.8
Shell Rg shell_rg43.00
Envelope Rg envelope_rg43.65
Shape Rg shape_rg42.44
Total Rg total_rg42.32
Total atoms total_atoms9223
Residues n_residues1156
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 dmax156.8
Rg (real space) rg_real42.81
Rg uncertainty (real space) rg_real_error1.82
I(0) (real space) i0_real2.5630e+08
I(0) uncertainty (real space) i0_real_error5.0200e+06
Rg (reciprocal space) rg_reciprocal42.08
I(0) (reciprocal space) i0_reciprocal256100000.0000
Solution quality estimate total_estimate0.7312
Solution quality rating solution_quality REASONABLE a REASONABLE solution
P(r) peaks n_peaks1
Primary peak position r_peak_primary37.1
Skewness Skewness skewness0.809
Kurtosis Kurtosis kurtosis0.122
Angular range angular_range— – 0.1900 −1
Current regularization parameter α current_alpha0.0001
Highest regularization parameter α highest_alpha39610000.0000
Real-space data points n_real_points39
GNOM version gnom_version4.1.3
Quality Criteria quality_criteria AN1: 0.000; Oscil: 0.406; Stabil: 1.000; Sysdev: 1.000; Positv: 1.000; Valcen: 0.608; Smooth: 0.677

5. Crystallography and Experiment 5. Crystallography & Experiment

6. Entities and Polymers Entities & Polymers (6)

7. Fold Classification (SCOP + CATH) 3 domains

CATH v4.4 (3 domains)

Domain ID domain_id7vbiB01
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_id7vbiN01
Class class2 — Mainly Beta
Architecture architecture60 — Sandwich
Topology topology40 — Immunoglobulin-like
Homologous superfamily homologous superfamily10 — Immunoglobulins
Domain ID domain_id7vbiR01
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)