8Z5P

human phosphorylase kinase - inactive state

これはPDB形式変換不可エントリーです。

8Z5P の概要

• エントリーDOI: 10.2210/pdb8z5p/pdb
• EMDBエントリー: 39777
• 分子名称: Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform, Phosphorylase b kinase regulatory subunit beta, Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform, ... (4 entities in total)
• 機能のキーワード: kinase, glycogenolysis, signaling protein, cytosolic protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 653017.28

構造登録者

Ma, R.,Yan, K. (登録日: 2024-04-18, 公開日: 2025-04-23, 最終更新日: 2025-09-24)

主引用文献

Ma, R.,Du, B.,Shi, C.,Wang, L.,Zeng, F.,Han, J.,Guan, H.,Wang, Y.,Yan, K.
Molecular basis for the regulation of human phosphorylase kinase by phosphorylation and Ca 2.
Nat Commun, 16:3020-3020, 2025

PubMed Abstract: Phosphorylase kinase (PhK) regulates the degradation of glycogen by integrating diverse signals, providing energy to the organism. Dysfunctional mutations may directly lead to Glycogen Storage Disease type IX (GSD IX), whereas the abnormal expression of PhK is also associated with tumors. Here, we use cryo-electron microscopy (cryo-EM) to resolve its near-atomic structures in the inactive and active states. These structures reveal the interactions and relative locations of the four subunits (αβγδ) within the PhK complex. Phosphorylated α and β subunits induce PhK to present a more compact state, while Ca causes sliding of the δ subunit along the helix of the γ subunit. Both actions synergistically activate PhK by enabling the de-inhibition of the γ subunit. We also identified different binding modes between PhK and its substrate, glycogen phosphorylase (GP), in two distinct states, using cross-linking mass spectrometry (XL-MS). This study provides valuable insights into the regulatory mechanisms of PhK, thereby enhancing our understanding of GSD IX and its implications in tumorigenesis.

PubMed: 40148320
DOI: 10.1038/s41467-025-58363-8

実験手法

ELECTRON MICROSCOPY (3.41 Å)