4MX3

Crystal Structure of PKA RIalpha Homodimer

4MX3 の概要

• エントリーDOI: 10.2210/pdb4mx3/pdb
• 関連するPDBエントリー: 1NE4 1NE6 1RGS
• 分子名称: cAMP-dependent protein kinase type I-alpha regulatory subunit, ADENOSINE-3',5'-CYCLIC-MONOPHOSPHATE (2 entities in total)
• 機能のキーワード: pka, rialpha homodimer, cooperative camp binding, carney complex disease, signaling protein
• 由来する生物種: Bos taurus (bovine,cow,domestic cattle,domestic cow)
• 細胞内の位置: Cell membrane (By similarity): P00514
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 86949.67

構造登録者

Bruystens, J.G.H.,Wu, J.,Fortezzo, A.,Kornev, A.P.,Blumenthal, D.A.,Taylor, S.S. (登録日: 2013-09-25, 公開日: 2014-01-15, 最終更新日: 2023-09-20)

主引用文献

Bruystens, J.G.,Wu, J.,Fortezzo, A.,Kornev, A.P.,Blumenthal, D.K.,Taylor, S.S.
PKA RI alpha Homodimer Structure Reveals an Intermolecular Interface with Implications for Cooperative cAMP Binding and Carney Complex Disease.
Structure, 22:59-69, 2014

PubMed Abstract: The regulatory (R) subunit is the cAMP receptor of protein kinase A. Following cAMP binding, the inactive PKA holoenzyme complex separates into two active catalytic (C) subunits and a cAMP-bound R dimer. Thus far, only monomeric R structures have been solved, which fell short in explaining differences of cAMP binding for the full-length protein as compared to the truncated R subunits. Here we solved a full-length R-dimer structure that reflects the biologically relevant conformation, and this structure agrees well with small angle X-ray scattering. An isoform-specific interface is revealed between the protomers. This interface acts as an intermolecular sensor for cAMP and explains the cooperative character of cAMP binding to the RIα dimer. Mutagenesis of residues on this interface not only leads to structural and biochemical changes, but is also linked to Carney complex disease.

PubMed: 24316401
DOI: 10.1016/j.str.2013.10.012

実験手法

X-RAY DIFFRACTION (3.88 Å)