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

3UZS の概要

• エントリーDOI: 10.2210/pdb3uzs/pdb
• 関連するPDBエントリー: 1OMW 3UZT
• 分子名称: 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)
• 機能のキーワード: 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
• 由来する生物種: Bos taurus (bovine); 詳細
• 細胞内の位置: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): P63212
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 134677.33

構造登録者

Tesmer, J.J.G.,Tesmer, V.M. (登録日: 2011-12-07, 公開日: 2012-07-11, 最終更新日: 2023-09-13)

主引用文献

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

実験手法

X-RAY DIFFRACTION (4.52 Å)