ORCID

0009-0003-3769-1327

Keywords

Chaperone, Disaggregase, Amyloid, Cholera toxin, Neurodegeneration

Abstract

Protein disulfide isomerase (PDI) is an essential, multifunctional, and promiscuous protein with a modular abb’xa’c domain arrangement. Conformational flexibility and the independent, yet coordinated, functionality of PDI domains facilitate protein folding, redox regulation, and the maintenance of cellular homeostasis. Previous investigations have shown that PDI can inhibit amyloid β peptide aggregation, associated with Alzheimer's disease, and is required for cholera toxin disassembly, the rate-limiting step in Vibrio cholerae pathogenesis. However, the precise mechanistic details underlying these interactions remain to be elucidated. Using molecular and biophysical approaches, this study has begun to establish substrate-induced unfolding, or conditional disorder, of PDI as the molecular basis for its observed disaggregase activity. This project proposes a unified mechanistic framework describing how PDI’s structural flexibility underlies its substrate-specific disaggregase function, offering novel insights into chaperone biology, toxin biology, and neurobiology. The significance of this research lies in highlighting PDI as a molecular target for therapeutic intervention in neurodegenerative disease and V. cholerae infection.

Completion Date

2025

Semester

Summer

Committee Chair

Teter, Ken; Tatulian, Suren

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Format

PDF

Identifier

DP0029588

Language

English

Document Type

Thesis

Campus Location

Orlando (Main) Campus

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