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- W4386090470 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 + -induced pinching of intracellular helical segments. Thus, our findings illuminate the energetics and ion coupling stoichiometries of PTCH1 transport mechanisms, whereby one to three Na + or two to three K + couple to cholesterol export, and provide the first molecular description of transitions between distinct transport states." @default.
- W4386090470 created "2023-08-24" @default.
- W4386090470 creator A5013028120 @default.
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- W4386090470 creator A5041718990 @default.
- W4386090470 creator A5055546235 @default.
- W4386090470 creator A5076214491 @default.
- W4386090470 date "2023-08-25" @default.
- W4386090470 modified "2023-10-02" @default.
- W4386090470 title "The energetics and ion coupling of cholesterol transport through Patched1" @default.
- W4386090470 cites W1031578623 @default.
- W4386090470 cites W1493374012 @default.
- W4386090470 cites W1558826482 @default.
- W4386090470 cites W1595347157 @default.
- W4386090470 cites W1964758803 @default.
- W4386090470 cites W1982824007 @default.
- W4386090470 cites W1986986500 @default.
- W4386090470 cites W1991794210 @default.
- W4386090470 cites W1993416164 @default.
- W4386090470 cites W2024762727 @default.
- W4386090470 cites W2026073246 @default.
- W4386090470 cites W2029667189 @default.
- W4386090470 cites W2031234765 @default.
- W4386090470 cites W2035687084 @default.
- W4386090470 cites W2036847375 @default.
- W4386090470 cites W2041638382 @default.
- W4386090470 cites W2043810467 @default.
- W4386090470 cites W2056994384 @default.
- W4386090470 cites W2057477511 @default.
- W4386090470 cites W2062337964 @default.
- W4386090470 cites W2063206968 @default.
- W4386090470 cites W2067200099 @default.
- W4386090470 cites W2070184849 @default.
- W4386090470 cites W2079823690 @default.
- W4386090470 cites W2081693079 @default.
- W4386090470 cites W2108444995 @default.
- W4386090470 cites W2109154308 @default.
- W4386090470 cites W2109976541 @default.
- W4386090470 cites W2112591804 @default.
- W4386090470 cites W2117458899 @default.
- W4386090470 cites W2119267663 @default.
- W4386090470 cites W2122590911 @default.
- W4386090470 cites W2123936150 @default.
- W4386090470 cites W2128572087 @default.
- W4386090470 cites W2141273392 @default.
- W4386090470 cites W2142532813 @default.
- W4386090470 cites W2146156622 @default.
- W4386090470 cites W2146411229 @default.
- W4386090470 cites W2168269595 @default.
- W4386090470 cites W2221824803 @default.
- W4386090470 cites W2314292783 @default.
- W4386090470 cites W2327174080 @default.
- W4386090470 cites W2327581403 @default.
- W4386090470 cites W2396636851 @default.
- W4386090470 cites W2405075761 @default.
- W4386090470 cites W2439567776 @default.
- W4386090470 cites W2522948027 @default.
- W4386090470 cites W2594464065 @default.
- W4386090470 cites W2744732181 @default.
- W4386090470 cites W2759174255 @default.
- W4386090470 cites W2775628882 @default.
- W4386090470 cites W2791375569 @default.
- W4386090470 cites W2794694420 @default.
- W4386090470 cites W2809141540 @default.
- W4386090470 cites W2811347531 @default.
- W4386090470 cites W2813910014 @default.
- W4386090470 cites W2859185793 @default.
- W4386090470 cites W2888579822 @default.
- W4386090470 cites W2892113269 @default.
- W4386090470 cites W2901641202 @default.
- W4386090470 cites W2901664208 @default.
- W4386090470 cites W2905232362 @default.
- W4386090470 cites W2910356247 @default.
- W4386090470 cites W2913841228 @default.
- W4386090470 cites W2920711227 @default.
- W4386090470 cites W2945843914 @default.
- W4386090470 cites W2949657777 @default.
- W4386090470 cites W2950624856 @default.
- W4386090470 cites W2955291917 @default.
- W4386090470 cites W2963699952 @default.
- W4386090470 cites W2971793051 @default.
- W4386090470 cites W2973505555 @default.
- W4386090470 cites W2974282989 @default.
- W4386090470 cites W2974791834 @default.
- W4386090470 cites W2982151985 @default.
- W4386090470 cites W2995816366 @default.
- W4386090470 cites W2999269724 @default.
- W4386090470 cites W3010340553 @default.
- W4386090470 cites W3082842604 @default.
- W4386090470 cites W3096678867 @default.
- W4386090470 cites W3102357733 @default.
- W4386090470 cites W3111206976 @default.
- W4386090470 cites W3177243041 @default.
- W4386090470 cites W3208262996 @default.
- W4386090470 cites W3209305865 @default.
- W4386090470 cites W4205616329 @default.
- W4386090470 cites W4210276647 @default.
- W4386090470 cites W4214493999 @default.