RESEARCH: MEMBRANE TRANSPORT
FOLDING PROJECT #15225 PROFILE

This project studies how mutations affect the NPC1 protein, which helps transport stuff within cells. Some mutations cause the protein to break down, leading to Niemann-Pick disease. By looking at mutations that fix this problem, we can learn what parts of the protein are important for its shape and function.

Note: This TLDR is a simplication and may not be 100% accurate.

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.

Mutations are changes in the genetic code (DNA) that can alter protein function or structure. They can be inherited or occur spontaneously and contribute to various diseases.

---

protein

Large biomolecules composed of chains of amino acids.

Proteins are essential for life, carrying out a vast array of functions within cells. They act as enzymes, structural components, hormones, and transporters.

---

lysosome

Membrane-bound organelles responsible for cellular waste disposal and recycling.

Lysosomes are membrane-enclosed compartments within cells that contain enzymes to break down various materials. They play a crucial role in removing waste products and recycling cellular components.

---

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 within cells. It plays a crucial role in synthesizing proteins and lipids, folding and modifying proteins, and transporting molecules.

---

NPC1

Niemann-Pick type C1 protein

NPC1 is a protein essential for the proper functioning of lysosomes. Mutations in the NPC1 gene can lead to Niemann-Pick type C disease, a rare genetic disorder characterized by the accumulation of cholesterol and other lipids in cells.

---

Niemann-Pick type C disease

A rare genetic disorder characterized by the accumulation of cholesterol and other lipids in cells.

Niemann-Pick type C disease is a lysosomal storage disorder caused by mutations in genes responsible for transporting cholesterol. It leads to progressive neurological deterioration, liver dysfunction, and other symptoms.

---

mutation

A permanent alteration in the DNA sequence.

Mutations are changes in the genetic code (DNA) that can alter protein function or structure. They can be inherited or occur spontaneously and contribute to various diseases.