ArticleBiophysical journal2015
Characterization of PROPPIN-Phosphoinositide Binding and Role of Loop 6CD in PROPPIN-Membrane Binding.
Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 52 citations in OpenAlex.
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- WIPI2b recruitment to phagophores and ATG16L1 binding are regulated by ULK1 phosphorylation.EMBO reports · 2024Article
- Atg18 oligomer organization in assembled tubes and on lipid membrane scaffolds.Nature communications · 2023Article
- Membrane curvature sensing and stabilization by the autophagic LC3 lipidation machinery.Science advances · 2022Article
- Review
- CROP: a retromer-PROPPIN complex mediating membrane fission in the endo-lysosomal system.The EMBO journal · 2022Article
- Theater in the Self-Cleaning Cell: Intrinsically Disordered Proteins or Protein Regions Acting with Membranes in Autophagy.Membranes · 2022Review
- In silico investigation of Alsin RLD conformational dynamics and phosphoinositides binding mechanism.PloS one · 2022Article
- WIPI1 promotes fission of endosomal transport carriers and formation of autophagosomes through distinct mechanisms.Autophagy · 2021Article
- Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Small but mighty: Atg8s and Rabs in membrane dynamics during autophagy.Biochimica et biophysica acta. Molecular cell research · 2021Review
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- The crystal structure of Atg18 reveals a new binding site for Atg2 in Saccharomyces cerevisiae.Cellular and molecular life sciences : CMLS · 2021Article
- Wipi3 is essential for alternative autophagy and its loss causes neurodegeneration.Nature communications · 2020Article
- Emerging roles of ATG proteins and membrane lipids in autophagosome formation.Cell discovery · 2020Review
- The expanding spectrum of neurological disorders of phosphoinositide metabolism.Disease models & mechanisms · 2019Review
- Preferential phosphatidylinositol 5-phosphate binding contributes to a destabilization of the VHS domain structure of Tom1.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PROPPINs (β-propellers that bind polyphosphoinositides) are a family of PtdIns3P- and PtdIns(3,5)P2-binding proteins that play an important role in autophagy. We analyzed PROPPIN-membrane binding through isothermal titration calorimetry (ITC), stopped-flow measurements, mutagenesis studies, and molecular dynamics (MD) simulations. ITC measurements showed that the yeast PROPPIN family members Atg18, Atg21, and Hsv2 bind PtdIns3P and PtdIns(3,5)P2 with high affinities in the nanomolar to low-micromolar range and have two phosphoinositide (PIP)-binding sites. Single PIP-binding site mutants have a 15- to 30-fold reduced affinity, which explains the requirement of two PIP-binding sites in PROPPINs. Hsv2 bound small unilamellar vesicles with a higher affinity than it bound large unilamellar vesicles in stopped-flow measurements. Thus, we conclude that PROPPIN membrane binding is curvature dependent. MD simulations revealed that loop 6CD is an anchor for membrane binding, as it is the region of the protein that inserts most deeply into the lipid bilayer. Mutagenesis studies showed that both hydrophobic and electrostatic interactions are required for membrane insertion of loop 6CD. We propose a model for PROPPIN-membrane binding in which PROPPINs are initially targeted to membranes through nonspecific electrostatic interactions and are then retained at the membrane through PIP binding.
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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.