RESEARCH: MEMBRANE TRANSPORT
FOLDING PROJECT #15226 PROFILE

This project studies how changes to the NPC1 protein cause a disease called Niemann-Pick type C1. The goal is to find out which parts of the protein are important for its shape and ability to work properly inside cells. By making specific changes to the protein, researchers hope to understand how to fix these problems and potentially develop treatments for this disease.

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.

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Niemann-Pick type C1 protein

A protein involved in lipid transport within lysosomes.

The Niemann-Pick type C1 protein (NPC1) is crucial for transporting cholesterol and other lipids within the lysosome, a cellular compartment responsible for breaking down waste materials. Mutations in this gene can lead to Niemann-Pick type C disease, characterized by lipid accumulation and damage to various organs.

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NPC1

Niemann-Pick type C1 protein

NPC1 is a common abbreviation for the Niemann-Pick type C1 protein, a vital enzyme involved in lipid transport within lysosomes. Mutations in this gene can cause Niemann-Pick type C disease.

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mutation

A permanent alteration in the DNA sequence.

A mutation is a change in the DNA sequence that makes up a gene. These changes can be small, affecting only a single nucleotide, or large, involving entire sections of chromosomes. Mutations can have various effects, ranging from being harmless to causing disease.

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lysosome

A membrane-bound organelle responsible for intracellular digestion.

Lysosomes are specialized compartments within cells that act as recycling centers. They contain powerful enzymes that break down waste materials, cellular debris, and engulfed pathogens. This process is essential for maintaining cellular health and homeostasis.

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endoplasmic reticulum

A network of membranes involved in protein synthesis and folding.

The endoplasmic reticulum (ER) is a complex network of interconnected membrane sacs and tubules that plays a vital role in protein synthesis, folding, modification, and transport. It's essential for producing proteins destined for secretion or integration into cellular membranes.

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protein misfolding

Incorrect folding of a protein due to genetic mutations or environmental stress.

Protein misfolding occurs when proteins fail to achieve their correct three-dimensional shape. This can disrupt their function and lead to various diseases, such as Alzheimer's disease and cystic fibrosis.

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membrane transporter

A protein that facilitates the movement of molecules across cell membranes.

Membrane transporters are specialized proteins embedded in cell membranes that regulate the passage of specific molecules into and out of cells. They play a crucial role in maintaining cellular homeostasis and transporting essential nutrients.