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Electrostatic Regulation of Phospholipase C β
Author(s) -
Esquina Candi,
Rugema Ngango Yvon,
GarlandKuntz Elisabeth,
Lyon Angeline
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.816.7
Subject(s) - diacylglycerol kinase , linker , microbiology and biotechnology , second messenger system , phospholipase c , subfamily , chemistry , biochemistry , biophysics , enzyme activator , phospholipase , cytoplasm , enzyme , biology , protein kinase c , gene , computer science , operating system
Phospholipase C (PLC) is an enzyme class that cleaves phosphatindylinositol lipids from cellular membranes to produce second messengers, including inositol‐1,4,5‐triphosphate (IP 3 ) and diacylglycerol (DAG). The PLCβ subfamily is among the best characterized of the PLC super family and is crucial for normal cardiovascular function. Under basal conditions, PLCβ has very low basal activity and is partitioned between the plasma membrane and the cytoplasm. However, it is still unclear how this low activity is maintained from a molecular standpoint. One known autoinhibitory element is the X–Y linker, a loop within the catalytic domain that forms a lid over the active site and participates in interfacial activation. Autoinhibition is thought to require a highly conserved acidic stretch within the linker, as deletions encompassing this region, or the entire linker, result in increased basal activity, decreased efficacy of G protein activation, and decreased thermal stability. These results, together with previous structural studies, suggest that the acidic stretch may regulate activity in part through interactions with conserved basic residues on adjacent surfaces of the catalytic domain. We are using site‐directed mutagenesis, functional assays, and structural studies to establish the contribution of electrostatic interactions to understand how these interactions play a role in the regulation of PLCβ. Support or Funding Information Purdue University start‐up funds