Date of Award
Doctor of Philosophy (PhD)
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.
Chair and Committee
Michael L. Gross
Jeffrey P. Henderson, John-Stephen Taylor, Meredith Jackrel, Timothy Wencewicz,
Guo, Chunyang, "Integrated Mass Spectrometry-Based Method in Protein Chemistry: Metal-binding Protein and Integral Membrane Protein" (2021). Arts & Sciences Electronic Theses and Dissertations. 2420.