Abstract:
: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 ShhNC24II, 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.
journal_name
Sci Advjournal_title
Science advancesauthors
Qi C,Di Minin G,Vercellino I,Wutz A,Korkhov VMdoi
10.1126/sciadv.aaw6490subject
Has Abstractpub_date
2019-09-18 00:00:00pages
eaaw6490issue
9issn
2375-2548pii
aaw6490journal_volume
5pub_type
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