Intramolecular electrostatic interactions contribute to phospholipase Cβ3 autoinhibition.

ABSTRACT: Phospholipase Cβ (PLCβ) enzymes regulate second messenger production following the activation of G protein-coupled receptors (GPCRs). Under basal conditions, these enzymes are maintained in an autoinhibited state by multiple elements, including an insertion within the catalytic domain known as the X-Y linker. Although the PLCβ X-Y linker is variable in sequence and length, its C-terminus is conserved and features an acidic stretch, followed by a short helix. This helix interacts with residues near the active site, acting as a lid to sterically prevent substrate binding. However, deletions that remove the acidic stretch of the X-Y linker increase basal activity to the same extent as deletion of the entire X-Y linker. Thus, the acidic stretch may be the linchpin in autoinhibition mediated by

SUBMITTER: Esquina CM 

PROVIDER: S-EPMC6686194 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature