ArticleCellular signalling2019
Intramolecular electrostatic interactions contribute to phospholipase Cβ3 autoinhibition.
Article in Cellular signalling, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- A catalytically competent sperm PLCzeta variant causes fertilization failure through protein insufficiency.Journal of assisted reproduction and genetics · 2026Article
- Cryo-EM structure of phospholipase Cε defines N-terminal domains and their roles in activity.Communications biology · 2025Article
- RhoA allosterically activates phospholipase Cε via its EF hands.Communications biology · 2025Article
- Competition between Nucleic Acids and Intrinsically Disordered Regions within Proteins.Accounts of chemical research · 2025Article
- Protein disorder and autoinhibition: The role of multivalency and effective concentration.Current opinion in structural biology · 2023Review
- Negatively charged, intrinsically disordered regions can accelerate target search by DNA-binding proteins.Nucleic acids research · 2023Article
- Proteogenomic Analysis of Breast Cancer Transcriptomic and Proteomic Data, Using De Novo Transcript Assembly: Genome-Wide Identification of Novel Peptides and Clinical Implications.Molecular & cellular proteomics : MCP · 2022Article
- Uveal melanoma-associated mutations in PLCβ4 are constitutively activating and promote melanocyte proliferation and tumorigenesis.Science signaling · 2021Article
- Structure and regulation of phospholipase Cβ and ε at the membrane.Chemistry and physics of lipids · 2021Review
- Structure of phospholipase Cε reveals an integrated RA1 domain and previously unidentified regulatory elements.Communications biology · 2020Article
- GαBiochemistry · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors.
Funding
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 the X-Y linker. We used site-directed mutagenesis and biochemical assays to investigate the importance of this acidic charge in mediating PLCβ3 autoinhibition. Loss of the acidic charge in the X-Y linker increases basal activity and decreases stability, consistent with loss of autoinhibition. However, introduction of compensatory electrostatic mutations on the surface of the PLCβ3 catalytic domain restore activity to basal levels. Thus, intramolecular electrostatics modulate autoinhibition by the X-Y linker.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.