ArticleStructure (London, England : 1993)2014
Molecular mechanisms of phospholipase C β3 autoinhibition.
Article in Structure (London, England : 1993), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Small peptides derived from the autoinhibitory XY linker of phospholipase C-β isoforms inhibit enzyme activity and reduce inflammation.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- Deciphering a mechanistic basis for the pathological effect of the GNAO1 E246K variant in neurodevelopmental disorder.BBA advances · 2026Article
- RhoA allosterically activates phospholipase Cε via its EF hands.Communications biology · 2025Article
- A molecular mechanism to diversify CaNature communications · 2024Article
- Spatiotemporal Optical Control of Gαq-PLCβ Interactions.ACS synthetic biology · 2024Article
- The mechanism ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Expression of the C-Terminal Domain of Phospholipase Cβ3 Inhibits Signaling via Gαq-Coupled Receptors and Transient Receptor Potential Channels.International journal of molecular sciences · 2022Article
- Characterization of the membrane interactions of phospholipase Cγ reveals key features of the active enzyme.Science advances · 2022Article
- Uveal melanoma-associated mutations in PLCβ4 are constitutively activating and promote melanocyte proliferation and tumorigenesis.Science signaling · 2021Article
- Every Detail Matters. That Is, How the Interaction between Gα Proteins and Membrane Affects Their Function.Membranes · 2021Review
- Structure and regulation of phospholipase Cβ and ε at the membrane.Chemistry and physics of lipids · 2021Review
- Delineation of molecular determinants for FR900359 inhibition of GThe Journal of biological chemistry · 2020Article
- Structure of phospholipase Cε reveals an integrated RA1 domain and previously unidentified regulatory elements.Communications biology · 2020Article
- Intramolecular electrostatic interactions contribute to phospholipase Cβ3 autoinhibition.Cellular signalling · 2019Article
- GαBiochemistry · 2019Article
- Structural design principles that underlie the multi-specific interactions of GαScientific reports · 2019Article
- Structure of the C-terminal guanine nucleotide exchange factor module of Trio in an autoinhibited conformation reveals its oncogenic potential.Science signaling · 2019Article
- Direct observation of conformational dynamics of the PH domain in phospholipases Cϵ and β may contribute to subfamily-specific roles in regulation.The Journal of biological chemistry · 2018Article
- Tracing the evolution of the heterotrimeric G protein α subunit in Metazoa.BMC evolutionary biology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Phospholipase C β (PLCβ) enzymes are dramatically activated by heterotrimeric G proteins. Central to this response is the robust autoinhibition of PLCβ by the X-Y linker region within its catalytic core and by the Hα2' helix in the C-terminal extension of the enzyme. The molecular mechanism of each and their mutual dependence are poorly understood. Herein, it is shown that distinct regions within the X-Y linker have specific roles in regulating activity. Most important,an acidic stretch within the linker stabilizes a lid that occludes the active site, consistent with crystal structures of variants lacking this region. Inhibition by the Hα2' helix is independent of the X-Y linker and likely regulates activity by limiting membrane interaction of the catalytic core. Full activation of PLCβ thus requires multiple independent molecular events induced by membrane association of the catalytic core and by the binding of regulatory proteins.
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Registered trials
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.