"Native Mass Spectrometry: A Structural Biology Tool" - Vicki Wysocki - Georgia Tech
Vicki Wysocki
Professor and Department Chair
School of Chemistry and Biochemisty
Georgia Tech
Abstract
Characterization of the overall topology and inter-subunit contacts of protein complexes, and their assembly/ disassembly and unfolding pathways, is critical because protein complexes regulate key biological processes, including processes important in understanding and controlling disease. Tools to address structural biology problems continue to improve. Native mass spectrometry (nMS) and associated technologies such as ion mobility and variable temperature electrospray ionization are becoming increasingly important components of the structural biology toolbox. When the native mass spectrometry approach is used early or mid-course in a structural characterization project, it can provides answers quickly for small amounts of sample, even when heterogeneity is present. Integration of sample preparation/purification with effective dissociation methods (e.g., surface-induced dissociation, SID), ion mobility, and computational approaches provide a workflow that is enabling in biochemical, synthetic biology, and systems biology approaches. Native MS can determine whether a complex of interest exists in a single or multiple oligomeric states, and surface induced dissociation can provide characterization of topology/inter-subunit connectivity and other structural features. Examples will illustrate the coupling of surface collisions to electron capture charge reduction and charge detection mass spectrometry for the characterization of protein and nucleoprotein complexes, including glycoproteins and adeno-associated virus capsids. Native “complex down” structural proteomics will be illustrated and combines size exclusion chromatography, capillary zone electrophoresis, and surface induced dissociation.
Research
Research in the Wysocki group is categorized into four broad areas:(1) development and implementation of surface-induced dissociation onto commercial time-of-flight, Orbitrap and FT-ICR instruments, (2) development and application of native mass spectrometry-guided structural biology approaches, (3) multi-omics approaches to biomarker discovery, disease diagnosis and prognosis using proteomics and metabolomics methods coupled with genomics and transcriptomics, and (4) determination of peptide and other fragment ion structures by IR action spectroscopy.
Bio
Vicki Wysocki received her BS in Chemistry at Western Kentucky University in 1982 and her PhD in Chemistry at Purdue University in 1987. After doing postdoctoral work at Purdue and at the Naval Research Laboratory, she joined Virginia Commonwealth University as an Assistant Professor in 1990. She was promoted to Associate Professor in 1994. Vicki joined the University of Arizona in 1996 and was promoted to Professor in 2000. She was Chair of the Department of Chemistry and Biochemistry at Arizona. and joined OSU in August 2012 as an Ohio Eminent Scholar. Most recently she joined Georgia Tech in 2025 as a Professor and Chair of School of Chemistry and Biochemistry.
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