Date of Award
Summer 8-23-2025
Document Type
Dissertation
Degree Name
Ph.D. in Chemistry and Biochemistry
Organizational Unit
College of Natural Science and Mathematics, Chemistry and Biochemistry
First Advisor
Scott Horowitz
Copyright Statement / License for Reuse
All Rights Reserved.
Keywords
Nucleic acid, Protein folding, Chaperonins, G-quadruplex
Abstract
Many proteins have slow folding times in vitro that are physiologically untenable. To combat this challenge, ATP-dependent chaperonins are thought to possess the unique ability to catalyze protein folding. Performing quantitative model selection using protein folding and unfolding data, we here show that short nucleic acids containing Gquadruplex (G4) structure can also catalyze protein folding. Performing the experiments as a function of temperature demonstrates that the G4 reshapes the underlying driving forces of protein folding. To understand the structural basis of this catalytic activity, we introduce NMR method to solve the structures, at base-level resolution, of a multiconformer G4 with chaperone activity without chemical shift assignments. We then perform structure-function studies via mutation and chaperone assays to test the G4 properties important for chaperoning protein aggregation and protein folding. Together, our finding uncovers a previously underappreciated role for nucleic acid in proteostasis and offer a new strategy for studying nucleic acid structure-function relationship at residue level.
Copyright Date
8-2025
Publication Statement
Copyright is held by the author. User is responsible for all copyright compliance.
Rights Holder
Zijue Huang
Provenance
Received from ProQuest
File Format
application/pdf
Language
English (eng)
Extent
113 pgs
File Size
13.2 MB
Recommended Citation
Huang, Zijue, "Role of Nucleic Acids as Chaperones in Protein Folding" (2025). Electronic Theses and Dissertations. 2629.
https://digitalcommons.du.edu/etd/2629