Undergraduate Honors Thesis Projects

Date of Award

Spring 2026

Document Type

Honors Paper

Degree Name

Biochemistry and Molecular Biology-BS

Department

Biochemistry and Molecular Biology

Advisor

Dr. John Tansey

First Committee Member

Dr. John Tansey

Second Committee Member

Dr. Brandon Sinn

Third Committee Member

Dr. Amy Johnson

Keywords

Lipid, metabolism, Perilipin 5, lipid droplet

Subject Categories

Biochemistry | Biochemistry, Biophysics, and Structural Biology | Higher Education | Molecular Biology

Abstract

Neutral lipids in animal cells are stored in structures called lipid storage droplets (LD). LDs are found in nearly all tissues of the body, consisting of neutral lipids forming a hydrophobic core, surrounded by a monolayer of phospholipids. Within the monolayer are proteins, including the perilipin family of proteins which regulate the storage and release of lipids. One family member, perilipin 5, works to coordinate lipid storage and breakdown while linking LDs to mitochondria to enhance energy production and metabolic regulation. Using AlphaFold, we obtained a predicted structure of perilipin 5, consisting of a boot-like shape containing a four-helix bundle and a hydrophobic pocket analogous to what has been observed experimentally in perilipin 3. In silico modeling data indicates that the hydrophobic pocket of perilipin 5 likely binds to hydrophobic molecules such as diacylglycerol. To probe the function of the hydrophobic pocket further, a mutant variant of perilipin 5 was created by replacing a key tryptophan in the hydrophobic pocket with glycine (W388G). The mutant was expressed in CHO cells and localized to lipid storage droplets when examined using immunofluorescence microscopy. Similar observations were made with cells expressing wild type protein indicating that the mutant protein is likely properly folded and functional and can be used to probe the nature of the pocket. To further probe the function of this pocket we have synthesized a fluorescent diacylglycerol analog and will be using it to validate our predictions made using in silico modeling.

Licensing Permission

Copyright, all rights reserved. Fair Use

Acknowledgement 1

1

Acknowledgement 2

1

Available for download on Wednesday, April 23, 2031

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