This item is under embargo and not available online per the author's request. For access information, please visit http://libanswers.wustl.edu/faq/5640.

ORCID

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

Date of Award

Spring 5-15-2021

Author's School

Graduate School of Arts and Sciences

Author's Department

Chemistry

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

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.

Language

English (en)

Chair and Committee

Michael L. Gross

Committee Members

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

Available for download on Thursday, March 17, 2022

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