Architecture and activation of human muscle phosphorylase kinase.

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 α₄β₄γ₄δ₄ hexadecamer consists of a tetramer of tetramer, wherein four αβγδ modules are connected by the central β₄ 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. Ca²⁺-free calmodulin (δ-subunit) bin

SUBMITTER: Yang X 

PROVIDER: S-EPMC10978961 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature