Exploring SOD1 electron transfer, heterodimerization, and hetero-amyloid formation.

Cu, Zn Superoxide dismutase (SOD1) is an essential metalloenzyme that regulates superoxide radicals. Because SOD1 is a long-lived protein, it contains an intrinsic molecular clock, deamidation, that accumulates over time. Misfolding and aggregation of SOD1 have been linked to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and, more recently, Parkinson's disease. To investigate the molecular factors underlying these processes, this dissertation examines the protein from the inside out, focusing on three concepts: (i) the metal center, (ii) subunit swapping, and (iii) hetero-amyloid formation. In chapter two, I use an analytical method, “protein charge ladders”, to distinguish between electron transfer (ET) and proton-coupled electron transfer (PCET) in a binuclear copper center by directly measuring the change in protein net charge upon reduction/oxidation (ΔZ4ET). Chapter three explores a hyper-deamidated form of SOD1, containing five of the protein’s seven deamidations, and evaluates how this natural post-translational modification affects heterodimerization. Chapter four investigates how the aggregation propensity of WT is altered in the presence of two mutations that do not aggregate in vitro.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Doctoral

Grantor

Baylor University.

Year dc:date.issued

2025

Author dc:creator

• Gonzalez, Mayte, 1998-

Advisor dc:contributor.advisor

• Shaw, Bryan Francis, 1976-

• Superoxide dismutase (SOD1)
• Charge regulation.
• Proton-coupled electron transfer (PCET)
• Heterodimerization.
• Deamidation.
• Amyloid formation.

Statement dc:rights

• Baylor University works are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. Contact libraryquestions@baylor.edu for inquiries about permission.

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/2104/13922

OAI identifier oai:identifier

oai:baylor-ir.tdl.org:2104/13922