RESEARCH: MEMBRANE TRANSPORT
FOLDING PROJECT #15223 PROFILE

This project studies how changes in the NPC1 protein can cause Niemann-Pick type C1 disease. Some mutations prevent NPC1 from working properly and going to lysosomes, but other mutations can fix this. By studying these fixes, scientists hope to understand what parts of NPC1 are important for its shape and function.

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.

mutations

Changes in the DNA sequence of a gene.

Mutations are alterations in the genetic code that can lead to variations in protein structure and function. They can be inherited or arise spontaneously during cell division. Mutations play a crucial role in evolution and disease development.

Niemann-Pick type C1

A rare genetic disorder characterized by the accumulation of lipids in lysosomes.

Niemann-Pick type C1 disease is a debilitating genetic condition that affects the body's ability to break down cholesterol and other fats. This leads to the buildup of these substances within cells, causing progressive neurological damage.

protein

A large biomolecule composed of chains of amino acids.

Proteins are essential building blocks of all living organisms. They perform a wide range of functions, including catalyzing chemical reactions, transporting molecules, providing structural support, and regulating cellular processes.

lysosome

A membrane-bound organelle containing digestive enzymes.

Lysosomes are crucial cellular compartments that function as recycling centers. They break down waste materials, cellular debris, and ingested pathogens using a variety of hydrolytic enzymes.

endoplasmic reticulum

A network of interconnected membranes involved in protein synthesis and lipid metabolism.

The endoplasmic reticulum (ER) is a complex network of membrane-bound sacs and tubules found within eukaryotic cells. It plays a vital role in protein folding, modification, and transport, as well as lipid synthesis and detoxification.