ArticleScience advances2023
The energetics and ion coupling of cholesterol transport through Patched1.
Article in Science advances, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
- Pathophysiological significance of cholesterol in ciliopathies.Fujita medical journal · 2026Article
- Article
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Regulatory mechanisms governing GLI proteins in hedgehog signaling.Anatomical science international · 2025Review
- Conformational changes in the Niemann-Pick type C1 protein NCR1 drive sterol translocation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Patched1 (PTCH1) is a tumor suppressor protein of the mammalian Hedgehog (HH) signaling pathway, implicated in embryogenesis and tissue homeostasis. PTCH1 inhibits the G protein-coupled receptor Smoothened (SMO) via a debated mechanism involving modulating ciliary cholesterol accessibility. Using extensive molecular dynamics simulations and free energy calculations to evaluate cholesterol transport through PTCH1, we find an energetic barrier of ~15 to 20 kilojoule per mole for cholesterol export. In silico data are coupled to in vivo biochemical assays of PTCH1 mutants to probe coupling between cation binding sites, transmembrane motions, and PTCH1 activity. Using complementary simulations of Dispatched1, we find that transition between "inward-open" and solvent "occluded" states is accompanied by Na
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