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

Summary for 3UZS

• Entry DOI: 10.2210/pdb3uzs/pdb
• Related: 1OMW 3UZT
• Descriptor: Beta-adrenergic receptor kinase 1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (5 entities in total)
• Functional Keywords: protein-rna complex, protein kinase fold, rgs homology domain, pleckstrin homology domain, beta propeller, g protein-coupled receptor phosphorylation, rna aptamer, carboxymethylation, geranylgeranylation, transferase-rna complex, transferase/rna
• Biological source: Bos taurus (bovine); More
• Cellular location: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): P63212
• Total number of polymer chains: 4
• Total formula weight: 134677.33

Authors

Tesmer, J.J.G.,Tesmer, V.M. (deposition date: 2011-12-07, release date: 2012-07-11, Last modification date: 2023-09-13)

Primary citation

Tesmer, V.M.,Lennarz, S.,Mayer, G.,Tesmer, J.J.
Molecular mechanism for inhibition of g protein-coupled receptor kinase 2 by a selective RNA aptamer.
Structure, 20:1300-1309, 2012

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.

PubMed: 22727813
DOI: 10.1016/j.str.2012.05.002

Experimental method

X-RAY DIFFRACTION (4.52 Å)