RESEARCH: MEMBRANE TRANSPORT
FOLDING PROJECT #15220 PROFILE

This project looks at how changes in the NPC1 protein affect its shape and ability to work properly. The project will simulate changes that help NPC1 function better, revealing what parts of the protein are crucial for both structure and how it moves things around inside cells.

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.

---

mutations

Changes in the DNA sequence.

Mutations are alterations in the genetic code. They can be inherited or arise spontaneously. Mutations can have various effects on an organism, ranging from being harmless to causing disease.

---

Niemann-Pick type C1 protein

A lysosomal membrane protein involved in cholesterol transport.

Niemann-Pick type C1 protein (NPC1) is crucial for transporting cholesterol within cells. When it malfunctions due to mutations, it leads to Niemann-Pick type C disease, a rare genetic disorder characterized by the accumulation of cholesterol in various organs.

---

protein

A large biomolecule composed of amino acids.

Proteins are essential building blocks and functional molecules in all living organisms. They have diverse roles, including catalyzing reactions, transporting molecules, providing structural support, and regulating cellular processes.

---

lysosome

An organelle responsible for intracellular digestion.

Lysosomes are membrane-bound organelles found within cells. They contain enzymes that break down waste materials, cellular debris, and foreign substances, playing a vital role in maintaining cellular homeostasis.

---

endoplasmic reticulum

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

The endoplasmic reticulum (ER) is a complex network of membranes extending throughout the cytoplasm of eukaryotic cells. It plays crucial roles in protein folding, modification, and transport, as well as lipid synthesis.

---

mutation

A permanent alteration in the DNA sequence.

Mutations are changes in the genetic code that can affect an organism's characteristics. They can occur spontaneously or be induced by environmental factors.

---

localization

The process of a molecule or structure being positioned in a specific location.

Localization refers to the positioning of molecules or structures within cells or tissues. It plays a crucial role in cellular function and organization.

---

protein misfolding

When a protein fails to fold into its correct three-dimensional shape.

Protein misfolding occurs when proteins fail to achieve their proper three-dimensional structure. This can lead to dysfunction and disease.