ArticleNature structural & molecular biology2022
Structural basis of phosphatidylinositol 3-kinase C2α function.
Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- PI3Kδ is selectively inhibited by roginolisib by stabilizing the C-terminal helix kα12.Nature communications · 2026Article
- The multifaceted significance of phosphoinositides in endocytic trafficking.FEBS letters · 2026Review
- Prioritization of chemical scaffolds using the TDR Targets database: An integrative workflow for Trypanosoma cruzi drug discovery.PLoS neglected tropical diseases · 2026Article
- A GABARAP-PtdIns3K-C1 positive feedback loop at the heart of the phagophore nucleation.Nature communications · 2026Article
- A novel RAB5 binding site in human VPS34-CII that is likely the primordial site in eukaryotic evolution.eLife · 2026Article
- VPS34 in Autophagy, Cancer, and Cancer Therapy.Cells · 2026Review
- PIKI-1, a class II PI 3-kinase, functions in endocytic trafficking.PLoS genetics · 2026Article
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
- PIKI-1, a class II phosphatidylinositol 3-kinase, functions in endocytic trafficking.bioRxiv : the preprint server for biology · 2025Article
- CARM1 regulates tubulin autoregulation through PI3KC2α R175 methylation.Cell communication and signaling : CCS · 2025Article
- Making PI3K superfamily enzymes run faster.Advances in biological regulation · 2025Review
- Post-stroke hippocampal neurogenesis is impaired by microvascular dysfunction and PI3K signaling in cerebral amyloid angiopathy.Cell reports · 2024Article
- The class III phosphatidylinositol 3-kinase VPS34 supports EV71 replication by promoting viral replication organelle formation.Journal of virology · 2024Article
- Identification of Prognostic Markers and Potential Therapeutic Targets using Gene Expression Profiling and Simulation Studies in Pancreatic Cancer.Current computer-aided drug design · 2024Article
- The big chill: Growth ofQRB discovery · 2024Review
- Structural Basis for Highly Selective Class II Alpha Phosphoinositide-3-Kinase Inhibition.Journal of medicinal chemistry · 2023Article
- Multifaceted membrane interactions of human Atg3 promote LC3-phosphatidylethanolamine conjugation during autophagy.Nature communications · 2023Article
- Structural and mechanistic insights provided by single particle cryo-EM analysis of phosphoinositide 3-kinase (PI3Kα).Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- Unravelling the genetic framework associated with grain quality and yield-related traits in maize (Frontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphatidylinositol 3-kinase type 2α (PI3KC2α) is an essential member of the structurally unresolved class II PI3K family with crucial functions in lipid signaling, endocytosis, angiogenesis, viral replication, platelet formation and a role in mitosis. The molecular basis of these activities of PI3KC2α is poorly understood. Here, we report high-resolution crystal structures as well as a 4.4-Å cryogenic-electron microscopic (cryo-EM) structure of PI3KC2α in active and inactive conformations. We unravel a coincident mechanism of lipid-induced activation of PI3KC2α at membranes that involves large-scale repositioning of its Ras-binding and lipid-binding distal Phox-homology and C-C2 domains, and can serve as a model for the entire class II PI3K family. Moreover, we describe a PI3KC2α-specific helical bundle domain that underlies its scaffolding function at the mitotic spindle. Our results advance our understanding of PI3K biology and pave the way for the development of specific inhibitors of class II PI3K function with wide applications in biomedicine.
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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.