Simulations of NPC1(NTD):NPC2 Protein Complex Reveal Cholesterol Transfer Pathways.

ABSTRACT: The Niemann Pick type C (NPC) proteins, NPC1 and NPC2, are involved in the lysosomal storage disease, NPC disease. The formation of a NPC1⁻NPC2 protein⁻protein complex is believed to be necessary for the transfer of cholesterol and lipids out of the late endosomal (LE)/lysosomal (Lys) compartments. Mutations in either NPC1 or NPC2 can lead to an accumulation of cholesterol and lipids in the LE/Lys, the primary phenotype of the NPC disease. We investigated the NPC1(NTD)⁻NPC2 protein⁻protein complex computationally using two putative binding interfaces. A combination of molecular modeling and molecular dynamics simulations reveals atomic details that are responsible for interface stability. Cholesterol binding energies associated with each of the binding pockets for the two models are calcul

SUBMITTER: Hodoscek M 

PROVIDER: S-EPMC6163316 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature