8Z5M

human phosphorylase kinase alpha/gamma/delta subcomplex - inactive state

Summary for 8Z5M

• Entry DOI: 10.2210/pdb8z5m/pdb
• EMDB information: 39775
• Descriptor: Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform, Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform, Calmodulin-3 (3 entities in total)
• Functional Keywords: kinase, glycogenolysis, cytosolic protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 201475.68

Authors

Ma, R.,Yan, K. (deposition date: 2024-04-18, release date: 2025-04-23, Last modification date: 2025-09-24)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.66 Å)