8JFK

PhK holoenzyme in inactive state, muscle isoform

8JFK の概要

• エントリーDOI: 10.2210/pdb8jfk/pdb
• EMDBエントリー: 36212
• 分子名称: Phosphorylase b kinase regulatory subunit beta, Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform, Calmodulin-1, ... (5 entities in total)
• 機能のキーワード: glycogen phosphorylase b kinase, muscle isoform, inactive state, cytosolic protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 16
• 化学式量合計: 1299409.34

構造登録者

Yang, X.K.,Xiao, J.Y. (登録日: 2023-05-18, 公開日: 2024-04-03, 最終更新日: 2024-11-06)

主引用文献

Yang, X.,Zhu, M.,Lu, X.,Wang, Y.,Xiao, J.
Architecture and activation of human muscle phosphorylase kinase.
Nat Commun, 15:2719-2719, 2024

PubMed Abstract: The study of phosphorylase kinase (PhK)-regulated glycogen metabolism has contributed to the fundamental understanding of protein phosphorylation; however, the molecular mechanism of PhK remains poorly understood. Here we present the high-resolution cryo-electron microscopy structures of human muscle PhK. The 1.3-megadalton PhK αβγδ hexadecamer consists of a tetramer of tetramer, wherein four αβγδ modules are connected by the central β scaffold. The α- and β-subunits possess glucoamylase-like domains, but exhibit no detectable enzyme activities. The α-subunit serves as a bridge between the β-subunit and the γδ subcomplex, and facilitates the γ-subunit to adopt an autoinhibited state. Ca-free calmodulin (δ-subunit) binds to the γ-subunit in a compact conformation. Upon binding of Ca, a conformational change occurs, allowing for the de-inhibition of the γ-subunit through a spring-loaded mechanism. We also reveal an ADP-binding pocket in the β-subunit, which plays a role in allosterically enhancing PhK activity. These results provide molecular insights of this important kinase complex.

PubMed: 38548794
DOI: 10.1038/s41467-024-47049-2

実験手法

ELECTRON MICROSCOPY (2.9 Å)