Sepehr Dehghani-Ghahnaviyeh

Conformational switch of NPC1 epitomizes a lumen-to-membrane alternating access model for nonpolar substrates.

Niemann-Pick disease type C (NPC) arises from failure of the NPC1 and/or NPC2 proteins to mobilize lysosomal cholesterol, yet the mechanism by which the complex drives sterol translocation lacks a thorough understanding. Here, we capture an NPC1-NPC2 complex conformation at lysosomal pH using a bis-sterol ligand (JM046...