2QKH

Crystal structure of the extracellular domain of human GIP receptor in complex with the hormone GIP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.183 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.167 

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This is version 2.0 of the entry. See complete history


Literature

Crystal structure of the incretin-bound extracellular domain of a G protein-coupled receptor

Parthier, C.Kleinschmidt, M.Neumann, P.Rudolph, R.Manhart, S.Schlenzig, D.Fanghanel, J.Rahfeld, J.-U.Demuth, H.-U.Stubbs, M.T.

(2007) Proc Natl Acad Sci U S A 104: 13942-13947

  • DOI: https://doi.org/10.1073/pnas.0706404104
  • Primary Citation of Related Structures:  
    2QKH

  • PubMed Abstract: 

    Incretins, endogenous polypeptide hormones released in response to food intake, potentiate insulin secretion from pancreatic beta cells after oral glucose ingestion (the incretin effect). This response is signaled by the two peptide hormones glucose-dependent insulinotropic polypeptide (GIP) (also known as gastric inhibitory polypeptide) and glucagon-like peptide 1 through binding and activation of their cognate class 2 G protein-coupled receptors (GPCRs). Because the incretin effect is lost or significantly reduced in patients with type 2 diabetes mellitus, glucagon-like peptide 1 and GIP have attracted considerable attention for their potential in antidiabetic therapy. A paucity of structural information precludes a detailed understanding of the processes of hormone binding and receptor activation, hampering efforts to develop novel pharmaceuticals. Here we report the crystal structure of the complex of human GIP receptor extracellular domain (ECD) with its agonist, the incretin GIP(1-42). The hormone binds in an alpha-helical conformation in a surface groove of the ECD largely through hydrophobic interactions. The N-terminal ligand residues would remain free to interact with other parts of the receptor. Thermodynamic data suggest that binding is concomitant with structural organization of the hormone, resulting in a complex mode of receptor-ligand recognition. The presentation of a well structured, alpha-helical ligand by the ECD is expected to be conserved among other hormone receptors of this class.


  • Organizational Affiliation

    Institut für Biochemie und Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, D-06120 Halle (Saale), Germany.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Glucose-dependent insulinotropic polypeptideA [auth B]42N/AMutation(s): 0 
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P09681 (Homo sapiens)
Explore P09681 
Go to UniProtKB:  P09681
PHAROS:  P09681
GTEx:  ENSG00000159224 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP09681
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Glucose-dependent insulinotropic polypeptide receptorB [auth A]135Homo sapiensMutation(s): 0 
Gene Names: GIPR
Membrane Entity: Yes 
UniProt & NIH Common Fund Data Resources
Find proteins for P48546 (Homo sapiens)
Explore P48546 
Go to UniProtKB:  P48546
PHAROS:  P48546
GTEx:  ENSG00000010310 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP48546
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
Cyclic 2,3-di-O-methyl-alpha-D-glucopyranose-(1-4)-2-O-methyl-alpha-D-glucopyranose-(1-4)-2,6-di-O-methyl-alpha-D-glucopyranose-(1-4)-2-O-methyl-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose-(1-4)-3-O-methyl-alpha-D-glucopyranose
C
7N/A
Glycosylation Resources
GlyTouCan:  G04274SM
GlyCosmos:  G04274SM
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
TAR
Query on TAR

Download Ideal Coordinates CCD File 
D [auth A]D(-)-TARTARIC ACID
C4 H6 O6
FEWJPZIEWOKRBE-LWMBPPNESA-N
Biologically Interesting Molecules (External Reference) 1 Unique
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.90 Å
  • R-Value Free: 0.183 
  • R-Value Work: 0.166 
  • R-Value Observed: 0.167 
  • Space Group: H 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 84.007α = 90
b = 84.007β = 90
c = 180.947γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
DMphasing
REFMACrefinement
PDB_EXTRACTdata extraction
CrystalCleardata collection
HKL-2000data reduction
SHELXSphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-08-14
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2017-10-18
    Changes: Refinement description
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Database references, Derived calculations, Non-polymer description, Structure summary