Official Project Description
This project aims to reveal the structural interactions that are interrupted in loss-of-structure/loss-of-function mutations for the Niemann-Pick type C1 protein NPC1.
The mutation I1061T has been shown to cause the titular Niemann-Pick type C1 disease by disallowing localization of this lysosomal membrane protein to the lysosome, instead being degraded in the endoplasmic reticulum due to protein misfolding.
Supplementary mutations (on top of the disease-causing mutation) have been shown to recover this activity, and by proxy, the structural stability that allows NPC1 to localize to the lysosomal membrane.
Simulating mutations that recover both structure and function as well as mutations that recover structure only will help reveal the critical interactions necessary for structural stability as well as membrane transporter efficacy.