4X6Q

An Isoform-specific Myristylation Switch Targets RIIb PKA Holoenzymes to Membranes

4X6Q の概要

• エントリーDOI: 10.2210/pdb4x6q/pdb
• 関連するPDBエントリー: 4X6R
• 分子名称: cAMP-dependent protein kinase type II-beta regulatory subunit, cAMP-dependent protein kinase catalytic subunit alpha (3 entities in total)
• 機能のキーワード: pka, membrane binding, molecular switch, transferase
• 由来する生物種: Mus musculus (Mouse); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 86931.27

構造登録者

Zhang, P.,Ye, F.,Bastidas, A.C.,Kornev, A.P.,Ginsberg, M.H.,Taylor, S.S. (登録日: 2014-12-08, 公開日: 2015-07-22, 最終更新日: 2024-10-23)

主引用文献

Zhang, P.,Ye, F.,Bastidas, A.C.,Kornev, A.P.,Wu, J.,Ginsberg, M.H.,Taylor, S.S.
An Isoform-Specific Myristylation Switch Targets Type II PKA Holoenzymes to Membranes.
Structure, 23:1563-1572, 2015

PubMed Abstract: Cyclic AMP-dependent protein kinase (PKA) is regulated in part by N-terminal myristylation of its catalytic (C) subunit. Structural information about the role of myristylation in membrane targeting of PKA has been limited. In mammalian cells there are four functionally non-redundant PKA regulatory subunits (RIα, RIβ, RIIα, and RIIβ). PKA is assembled as an inactive R2C2 holoenzyme in cells. To explore the role of N-myristylation in membrane targeting of PKA holoenzymes, we solved crystal structures of RIα:myrC and RIIβ2:myrC2, and showed that the N-terminal myristylation site in the myrC serves as a flexible "switch" that can potentially be mobilized for membrane anchoring of RII, but not RI, holoenzymes. Furthermore, we synthesized nanodiscs and showed by electron microscopy that membrane targeting through the myristic acid is specific for the RII holoenzyme. This membrane-anchoring myristylation switch is independent of A Kinase Anchoring Proteins (AKAPs) that target PKA to membranes by other mechanisms.

PubMed: 26278174
DOI: 10.1016/j.str.2015.07.007

実験手法

X-RAY DIFFRACTION (2.52 Å)