RESEARCH: MEMBRANE TRANSPORT
FOLDING PROJECT #15224 PROFILE

This project studies how changes in the NPC1 protein can cause Niemann-Pick type C1 disease. The project relates to mutations that prevent the protein from working properly and how other mutations can fix this problem. By studying these changes, scientists hope to learn more about how proteins fold correctly and how they move within cells.

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.

mutation

A permanent alteration in the DNA sequence that makes up a gene.

A mutation is a change in the DNA code of a gene. These changes can be small or large and can affect how a gene functions. Mutations are responsible for genetic variation and can lead to diseases, but they also play a role in evolution.

NPC1

Niemann-Pick type C1 protein

NPC1 is a protein involved in the transport of cholesterol within cells. Mutations in the NPC1 gene can lead to Niemann-Pick type C disease, a rare genetic disorder that causes the accumulation of cholesterol and other lipids in various organs.

lysosome

A membrane-bound organelle within a cell that contains enzymes for breaking down waste materials and cellular debris.

Lysosomes are like the recycling centers of cells. They contain powerful enzymes that break down worn-out cell parts, foreign substances, and other waste products. This process is essential for maintaining cellular health and function.

endoplasmic reticulum

A complex network of membranes within a cell that plays a role in protein synthesis, folding, and transport.

The endoplasmic reticulum is a vast network of interconnected tubes and sacs found within cells. It has two main regions: the rough ER, studded with ribosomes involved in protein synthesis, and the smooth ER, which plays roles in lipid metabolism and detoxification.

protein misfolding

The incorrect folding of a protein into its three-dimensional structure.

Protein misfolding occurs when a protein does not fold correctly into its intended shape. This can lead to dysfunctional proteins that are unable to perform their normal roles, potentially causing diseases.