8JFK

PhK holoenzyme in inactive state, muscle isoform

Summary for 8JFK

• Entry DOI: 10.2210/pdb8jfk/pdb
• EMDB information: 36212
• Descriptor: Phosphorylase b kinase regulatory subunit beta, Phosphorylase b kinase regulatory subunit alpha, skeletal muscle isoform, Calmodulin-1, ... (5 entities in total)
• Functional Keywords: glycogen phosphorylase b kinase, muscle isoform, inactive state, cytosolic protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 16
• Total formula weight: 1299409.34

Authors

Yang, X.K.,Xiao, J.Y. (deposition date: 2023-05-18, release date: 2024-04-03, Last modification date: 2024-11-06)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.9 Å)