2QCS

A complex structure between the Catalytic and Regulatory subunit of Protein Kinase A that represents the inhibited state

2QCS の概要

• エントリーDOI: 10.2210/pdb2qcs/pdb
• 関連するPDBエントリー: 1APM 1NE4 1NE6 1RGS
• 分子名称: cAMP-dependent protein kinase, alpha-catalytic subunit, cAMP-dependent protein kinase type I-alpha regulatory subunit, MANGANESE (II) ION, ... (9 entities in total)
• 機能のキーワード: cyclic adenosine monophosphate, camp-dependent protein kinase, pka holoenzyme, cyclic nucleotide binding domain, protein-protein interaction, conformational change, protein binding, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Mus musculus (house mouse); 詳細
• 細胞内の位置: Cytoplasm . Isoform 2: Cell projection, cilium, flagellum : P05132; Cell membrane : P00514
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 75151.43

構造登録者

Kim, C.,Cheng, C.Y.,Saldanha, A.S.,Taylor, S.S. (登録日: 2007-06-19, 公開日: 2007-11-06, 最終更新日: 2023-08-30)

主引用文献

Kim, C.,Cheng, C.Y.,Saldanha, S.A.,Taylor, S.S.
PKA-I holoenzyme structure reveals a mechanism for cAMP-dependent activation.
Cell(Cambridge,Mass.), 130:1032-1043, 2007

PubMed Abstract: Protein kinase A (PKA) holoenzyme is one of the major receptors for cyclic adenosine monophosphate (cAMP), where an extracellular stimulus is translated into a signaling response. We report here the structure of a complex between the PKA catalytic subunit and a mutant RI regulatory subunit, RIalpha(91-379:R333K), containing both cAMP-binding domains. Upon binding to the catalytic subunit, RI undergoes a dramatic conformational change in which the two cAMP-binding domains uncouple and wrap around the large lobe of the catalytic subunit. This large conformational reorganization reveals the concerted mechanism required to bind and inhibit the catalytic subunit. The structure also reveals a holoenzyme-specific salt bridge between two conserved residues, Glu261 and Arg366, that tethers the two adenine capping residues far from their cAMP-binding sites. Mutagenesis of these residues demonstrates their importance for PKA activation. Our structural insights, combined with the mutagenesis results, provide a molecular mechanism for the ordered and cooperative activation of PKA by cAMP.

PubMed: 17889648
DOI: 10.1016/j.cell.2007.07.018

実験手法

X-RAY DIFFRACTION (2.2 Å)