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-Structure paper
タイトル | Structural basis of sterol recognition by human hedgehog receptor PTCH1. |
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ジャーナル・号・ページ | Sci Adv, Vol. 5, Issue 9, Page eaaw6490, Year 2019 |
掲載日 | 2019年9月18日 |
![]() | Chao Qi / Giulio Di Minin / Irene Vercellino / Anton Wutz / Volodymyr M Korkhov / ![]() |
PubMed 要旨 | Hedgehog signaling is central in embryonic development and tissue regeneration. Disruption of the pathway is linked to genetic diseases and cancer. Binding of the secreted ligand, Sonic hedgehog ...Hedgehog signaling is central in embryonic development and tissue regeneration. Disruption of the pathway is linked to genetic diseases and cancer. Binding of the secreted ligand, Sonic hedgehog (ShhN) to its receptor Patched (PTCH1) activates the signaling pathway. Here, we describe a 3.4-Å cryo-EM structure of the human PTCH1 bound to ShhN, a modified hedgehog ligand mimicking its palmitoylated form. The membrane-embedded part of PTCH1 is surrounded by 10 sterol molecules at the inner and outer lipid bilayer portion of the protein. The annular sterols interact at multiple sites with both the sterol-sensing domain (SSD) and the SSD-like domain (SSDL), which are located on opposite sides of PTCH1. The structure reveals a possible route for sterol translocation across the lipid bilayer by PTCH1 and homologous transporters. |
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手法 | EM (単粒子) |
解像度 | 3.3 - 3.4 Å |
構造データ | EMDB-4936, PDB-6rmg: ![]() EMDB-4939: |
化合物 | ![]() ChemComp-NAG: ![]() ChemComp-Y01: ![]() ChemComp-ZN: |
由来 |
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![]() | MEMBRANE PROTEIN / Patched / PTCH1 / Hedgehog / ShhN |