ArticleMolecular biology of the cell2011
Resurrection of a functional phosphatidylinositol transfer protein from a pseudo-Sec14 scaffold by directed evolution.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed.
- In vitro methods for measuring lipid binding, transfer and competitive displacement reactions by peripheral membrane proteins.Methods in enzymology · 2026Article
- SEC14-GOLD protein PATELLIN2 binds IRON-REGULATED TRANSPORTER1 linking root iron uptake to vitamin E.Plant physiology · 2023Article
- Role of SEC14-like phosphatidylinositol transfer proteins in membrane identity and dynamics.Frontiers in plant science · 2023Review
- Lipid transfer proteins and instructive regulation of lipid kinase activities: Implications for inositol lipid signaling and disease.Advances in biological regulation · 2020Review
- Lipid Exchangers: Cellular Functions and Mechanistic Links With Phosphoinositide Metabolism.Frontiers in cell and developmental biology · 2020Review
- Functional diversification of the chemical landscapes of yeast Sec14-like phosphatidylinositol transfer protein lipid-binding cavities.The Journal of biological chemistry · 2019Article
- Carnosine improves diabetic retinopathy via the MAPK/ERK pathway.Experimental and therapeutic medicine · 2019Article
- The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes.Journal of lipid research · 2019Review
- Article
- Polyphosphoinositide-Binding Domains: Insights from Peripheral Membrane and Lipid-Transfer Proteins.Advances in experimental medicine and biology · 2019Review
- Target Identification and Mechanism of Action of Picolinamide and Benzamide Chemotypes with Antifungal Properties.Cell chemical biology · 2018Article
- Dynamics and energetics of the mammalian phosphatidylinositol transfer protein phospholipid exchange cycle.The Journal of biological chemistry · 2017Article
- Sec14-like phosphatidylinositol transfer proteins and the biological landscape of phosphoinositide signaling in plants.Biochimica et biophysica acta · 2016Review
- Structural elements that govern Sec14-like PITP sensitivities to potent small molecule inhibitors.Journal of lipid research · 2016Article
- Phosphatidylinositol transfer proteins and instructive regulation of lipid kinase biology.Biochimica et biophysica acta · 2015Review
- Sec14-nodulin proteins and the patterning of phosphoinositide landmarks for developmental control of membrane morphogenesis.Molecular biology of the cell · 2015Article
- Sec14-like phosphatidylinositol-transfer proteins and diversification of phosphoinositide signalling outcomes.Biochemical Society transactions · 2014Article
- PITPs as targets for selectively interfering with phosphoinositide signaling in cells.Nature chemical biology · 2014Article
- Structural consequences of mutations to the α-tocopherol transfer protein associated with the neurodegenerative disease ataxia with vitamin E deficiency.Biochemistry · 2013Article
- Sec14 like PITPs couple lipid metabolism with phosphoinositide synthesis to regulate Golgi functionality.Sub-cellular biochemistry · 2012Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Sec14-superfamily proteins integrate the lipid metabolome with phosphoinositide synthesis and signaling via primed presentation of phosphatidylinositol (PtdIns) to PtdIns kinases. Sec14 action as a PtdIns-presentation scaffold requires heterotypic exchange of phosphatidylcholine (PtdCho) for PtdIns, or vice versa, in a poorly understood progression of regulated conformational transitions. We identify mutations that confer Sec14-like activities to a functionally inert pseudo-Sec14 (Sfh1), which seemingly conserves all of the structural requirements for Sec14 function. Unexpectedly, the "activation" phenotype results from alteration of residues conserved between Sfh1 and Sec14. Using biochemical and biophysical, structural, and computational approaches, we find the activation mechanism reconfigures atomic interactions between amino acid side chains and internal water in an unusual hydrophilic microenvironment within the hydrophobic Sfh1 ligand-binding cavity. These altered dynamics reconstitute a functional "gating module" that propagates conformational energy from within the hydrophobic pocket to the helical unit that gates pocket access. The net effect is enhanced rates of phospholipid-cycling into and out of the Sfh1* hydrophobic pocket. Taken together, the directed evolution approach reveals an unexpectedly flexible functional engineering of a Sec14-like PtdIns transfer protein-an engineering invisible to standard bioinformatic, crystallographic, and rational mutagenesis approaches.
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Registered trials
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