Structure of phospholipase Cε reveals an integrated RA1 domain and previously unidentified regulatory elements.

ABSTRACT: Phospholipase Cε (PLCε) generates lipid-derived second messengers at the plasma and perinuclear membranes in the cardiovascular system. It is activated in response to a wide variety of signals, such as those conveyed by Rap1A and Ras, through a mechanism that involves its C-terminal Ras association (RA) domains (RA1 and RA2). However, the complexity and size of PLCε has hindered its structural and functional analysis. Herein, we report the 2.7 Å crystal structure of the minimal fragment of PLCε that retains basal activity. This structure includes the RA1 domain, which forms extensive interactions with other core domains. A conserved amphipathic helix in the autoregulatory X-Y linker of PLCε is also revealed, which we show modulates activity in vitro and in cells. The studies provide the st

SUBMITTER: Rugema NY 

PROVIDER: S-EPMC7427993 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature