ArticleScience advances2021
Structure of the phosphoinositide 3-kinase (PI3K) p110γ-p101 complex reveals molecular mechanism of GPCR activation.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 59 citations in OpenAlex.
- Article
- Reconstitution of Ras-PI3Kγ membrane communication and feedback using light-induced signaling inputs.Nature communications · 2026Article
- Use of hydrogen deuterium exchange mass spectrometry in tandem with modern structural biology.The Biochemical journal · 2026Review
- Biophysical and aerodynamic properties of a peptide targeting the A-kinase anchoring function of PI3Kγ for pulmonary cAMP modulation.Scientific reports · 2026Article
- Article
- A computational study of cardiac glycosides from Vernonia amygdalina as PI3K inhibitors for targeting HER2 positive breast cancer.Journal of computer-aided molecular design · 2025Article
- Investigating the Interplay Between the Nrf2/Keap1/HO-1/SIRT-1 Pathway and the p75NTR/PI3K/Akt/MAPK Cascade in Neurological Disorders: Mechanistic Insights and Therapeutic Innovations.Molecular neurobiology · 2025Review
- Biolayer interferometry for measuring the kinetics of protein-protein interactions and nanobody binding.Nature protocols · 2025Review
- Making PI3K superfamily enzymes run faster.Advances in biological regulation · 2025Review
- Molecular Basis of Oncogenic PI3K Proteins.Cancers · 2024Review
- Prediction of immunotherapy response using mutations to cancer protein assemblies.Science advances · 2024Article
- Molecular basis for Gβγ-mediated activation of phosphoinositide 3-kinase γ.Nature structural & molecular biology · 2024Article
- Article
- Article
- HAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Interleukin-21 Influences Glioblastoma Course: Biological Mechanisms and Therapeutic Potential.Cells · 2023Review
- Structural and mechanistic insights provided by single particle cryo-EM analysis of phosphoinositide 3-kinase (PI3Kα).Biochimica et biophysica acta. Reviews on cancer · 2023Review
- Article
- Allosteric activation or inhibition of PI3Kγ mediated through conformational changes in the p110γ helical domain.bioRxiv : the preprint server for biology · 2023Article
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 4 countries.
Funding
Abstract
The class IB phosphoinositide 3-kinase (PI3K), PI3Kγ, is a master regulator of immune cell function and a promising drug target for both cancer and inflammatory diseases. Critical to PI3Kγ function is the association of the p110γ catalytic subunit to either a p101 or p84 regulatory subunit, which mediates activation by G protein-coupled receptors. Here, we report the cryo-electron microscopy structure of a heterodimeric PI3Kγ complex, p110γ-p101. This structure reveals a unique assembly of catalytic and regulatory subunits that is distinct from other class I PI3K complexes. p101 mediates activation through its Gβγ-binding domain, recruiting the heterodimer to the membrane and allowing for engagement of a secondary Gβγ-binding site in p110γ. Mutations at the p110γ-p101 and p110γ-adaptor binding domain interfaces enhanced Gβγ activation. A nanobody that specifically binds to the p101-Gβγ interface blocks activation, providing a novel tool to study and target p110γ-p101-specific signaling events in vivo.
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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.