3UZS

Structure of the C13.28 RNA Aptamer Bound to the G Protein-Coupled Receptor Kinase 2-Heterotrimeric G Protein Beta 1 and Gamma 2 Subunit Complex


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.52 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.188 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Molecular mechanism for inhibition of g protein-coupled receptor kinase 2 by a selective RNA aptamer.

Tesmer, V.M.Lennarz, S.Mayer, G.Tesmer, J.J.

(2012) Structure 20: 1300-1309

  • DOI: https://doi.org/10.1016/j.str.2012.05.002
  • Primary Citation of Related Structures:  
    3UZS, 3UZT

  • PubMed Abstract: 

    Cardiovascular homeostasis is maintained in part by the rapid desensitization of activated heptahelical receptors that have been phosphorylated by G protein-coupled receptor kinase 2 (GRK2). However, during chronic heart failure GRK2 is upregulated and believed to contribute to disease progression. We have determined crystallographic structures of GRK2 bound to an RNA aptamer that potently and selectively inhibits kinase activity. Key to the mechanism of inhibition is the positioning of an adenine nucleotide into the ATP-binding pocket and interactions with the basic αF-αG loop region of the GRK2 kinase domain. Constraints imposed on the RNA by the terminal stem of the aptamer also play a role. These results highlight how a high-affinity aptamer can be used to selectively trap a novel conformational state of a protein kinase.


  • Organizational Affiliation

    Life Sciences Institute, University of Michigan, 210 Washtenaw Avenue, Ann Arbor, MI 48109-2216, USA. tesmerjj@umich.edu


Macromolecules

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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Beta-adrenergic receptor kinase 1689Bos taurusMutation(s): 1 
Gene Names: ADRBK1GRK2
EC: 2.7.11.15
UniProt
Find proteins for P21146 (Bos taurus)
Explore P21146 
Go to UniProtKB:  P21146
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UniProt GroupP21146
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1340Bos taurusMutation(s): 0 
Gene Names: GNB1
UniProt
Find proteins for P62871 (Bos taurus)
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Go to UniProtKB:  P62871
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UniProt GroupP62871
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  • Reference Sequence
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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2C [auth G]74Bos taurusMutation(s): 0 
Gene Names: GNG2
UniProt
Find proteins for P63212 (Bos taurus)
Explore P63212 
Go to UniProtKB:  P63212
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UniProt GroupP63212
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  • Reference Sequence
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Entity ID: 4
MoleculeChains LengthOrganismImage
C13.28 RNA AptamerD [auth C]28N/A
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
MG
Query on MG

Download Ideal Coordinates CCD File 
E [auth A]MAGNESIUM ION
Mg
JLVVSXFLKOJNIY-UHFFFAOYSA-N
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
CMT
Query on CMT
C [auth G]L-PEPTIDE LINKINGC4 H9 N O2 SCYS
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 4.52 Å
  • R-Value Free: 0.268 
  • R-Value Work: 0.184 
  • R-Value Observed: 0.188 
  • Space Group: P 3 1 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 257.277α = 90
b = 257.277β = 90
c = 99.429γ = 120
Software Package:
Software NamePurpose
MAR345dtbdata collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-07-11
    Type: Initial release
  • Version 1.1: 2012-08-29
    Changes: Database references
  • Version 1.2: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description