Molecular dynamics study with mutation shows that N-terminal domain structural re-orientation in Niemann-Pick type C1 is required for proper alignment of cholesterol transport.

ABSTRACT: The lysosomal membrane protein Niemann-Pick type C1 (NPC1) and Niemann-Pick type C2 (NPC2) are main players of cholesterol control in the lysosome and it is known that the mutation on these proteins leads to the cholesterol trafficking-related neurodegenerative disease, which is called the NPC disease. The mutation R518W or R518Q on the NPC1 is one of the type of disease-related mutation that causes cholesterol transports to be cut in half, which results in the accumulation of cholesterol and lipids in the late endosomal/lysosomal compartment of the cell. Even though there has been significant progress with understanding the cholesterol transport by NPC1 in combination with NPC2, especially after the structural determination of the full-length NPC1 in 2016, many details such as the interac

SUBMITTER: Yoon HJ 

PROVIDER: S-EPMC7461377 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature