Structural basis of sterol recognition by human hedgehog receptor PTCH1.

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 Adv

journal_title

Science advances

authors

Qi C,Di Minin G,Vercellino I,Wutz A,Korkhov VM

doi

10.1126/sciadv.aaw6490

subject

Has Abstract

pub_date

2019-09-18 00:00:00

pages

eaaw6490

issue

9

issn

2375-2548

pii

aaw6490

journal_volume

5

pub_type

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