Year: 2024
Type: article
Abstract: The study of phosphorylase kinase (PhK)-regulated glycogen metabolism has contributed to the fundamental understanding of protein phosphorylation. Here we present the high-resolution cryo-electron microscopy structures of human muscle PhK. The 1.3-megadalton PhK α 4 β 4 γ 4 δ 4 hexadecamer consists of a tetramer of tetramer, wherein four αβγδ modules are connected by the central β 4 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 2+ -free calmodulin (δ-subunit) binds to the γ-subunit in a compact conformation. Upon binding of Ca 2+ , 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 unprecedented molecular insights of this important kinase complex.
Source: Nature Communications
Authors: Xiaoke Yang, Mingqi Zhu, Xue Lu, Yuxin Wang, Junyu Xiao
Language: English
Subfield: Biochemistry
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Award: G4683509601
OpenAlex ID: W4393277981