D101N: A Unique and Ill-understood Familial ALS-related SOD1 Mutant

Author

Analisa LottFollow

Publication Date

Fall 12-6-2024

Degree Level

B.S.

Program

Chemistry

First Advisor

Ahmad Galaleldeen

Second Advisor

Camille Langston

Document Type

Thesis

Medium

Manuscript

Abstract

Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease, with 90% of documented cases considered sporadic and about 10% showing a hereditary link; such cases are deemed as familial ALS (fALS). Superoxide dismutase (SOD), a copper-zinc binding enzyme that protects cells from damaging free radicals, has been linked to fALS with certain toxic gain of function mutations, such as the D101N mutant. The human SOD1 D101N mutant has been shown to be associated with rapidly progressing neurodegeneration yet is less prone to aggregation than similar mutants, but its deviation from wild-type (WT) SOD1 remains misunderstood.

Objective: Although the D101N mutant has undergone some characterization, some specifics remain unclear, including a lack of consensus on its classification as a wild-type-like (WTL) or metal-binding-region (MBR) mutant. Structural elucidation of D101N SOD1 is one method to better understand the characteristics of the D101N mutant, and it is predicted that the mutant falls into the WTL category.

Methods: The protein was purified, crystallized, and subjected to x-ray crystallography to determine its folding structure.

Results: The asparagine substitution did not significantly alter the folding of SOD1. It was concluded that the D101N SOD1 mutant can be classified as WTL in the context of fALS mutants.

Recommended Citation

Lott Analisa M. D101N: A Unique and Ill-understood Familial ALS-related SOD1 Mutant. Digital Commons at St. Mary’s University. 2024.

Creative Commons License

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