Abstract

Most biological processes are associated with protein catalysis. Characterizing protein structure, therefore, is crucial for understanding biological function. Mass spectrometry (MS)-based methods have emerged as a pivotal biophysical tool to interrogate protein structures; they can characterize protein-ligand/protein complexes that are refractory to conventional high-resolution means such as X-ray crystallography, Cryo-EM, and nuclear magnetic resonance (NMR) spectroscopy, in part owing to high molecular weight and significant flexibility. The integrated MS-based platform will provide topology and structural information of proteins from sketch to detail; native MS identifies protein complexes’ composition and stoichiometry; hydrogen-deuterium exchange MS (HDX-MS) detects the protein complexes’ dynamic change at the peptide-level and sometimes at the residue-level; protein footprinting coupled with MS pinpoints the binding site at residue-level via irreversible chemical changes. This thesis comprising eight chapters focuses on method development and application of integrated MS-based platform, using examples of metal-binding proteins and integral membrane proteins that illustrate challenges and solutions.

Committee Chair

Michael L. Gross

Committee Members

Jeffrey P. Henderson, John-Stephen Taylor, Meredith Jackrel, Timothy Wencewicz,

Degree

Doctor of Philosophy (PhD)

Author's Department

Chemistry

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

Spring 5-15-2021

Language

English (en)

Author's ORCID

http://orcid.org/0000-0002-3600-8157

Included in

Chemistry Commons

Share

COinS