Ontology highlight
ABSTRACT:
SUBMITTER: Ansell TB
PROVIDER: S-EPMC10446486 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
Ansell T Bertie TB Corey Robin A RA Viti Lucrezia Vittoria LV Kinnebrew Maia M Rohatgi Rajat R Siebold Christian C Sansom Mark S P MSP
Science advances 20230823 34
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 ...[more]