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Thursday, January 23, 2014

From The Top Down: Mass Spectrometry and Its Role In Studying Intact Proteins and Protein Complex Structure, Dynamics, and Assembly

Moses Gomberg Analytical Lecture
1640 Chemistry
4:00 PM - 5:30 PM
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Speaker:   Albert Heck, Utrecht University
Abstract:   Around for more than a century the analytical technique of mass spectrometry is blooming more than ever, and applied in nearly all aspects of the natural and life sciences. In the last two decades mass spectrometry has become routine for the high-throughput analysis of peptides, lipids, glycan and other biomolecules. However, also intact proteins and even complete protein complexes can nowadays be analyzed, enabling MS to penetrate the field of structural biology. Here, I will describe the emerging role of mass spectrometry with its different technical facets in structural biology, focusing especially on the analysis of viruses, dynamic protein assemblies and therapeutic antibodies. I will describe how mass spectrometry has evolved into a tool that can provide unique structural and functional information about viral protein and protein complex structure, conformation, assembly and topology, extending to the direct analysis of intact virus capsids of several million Da in mass. Mass spectrometry is now used to address important questions in virology ranging from virus structural topology to how viruses assemble. The unique features of native MS will further be highlighted in a study of the macromolecular complex controlling circadian timing in cyanobacteria. I will also describe recent developments in mass spectrometry technology that have allowed us to analyze intact native proteins and protein complexes using Q-ToF and Orbitrap mass analyzers with very high sensitivity and mass resolving power, and how that has enabled us to profile therapeutic antibody quality and structure in their native state without requiring any sample preparation. Prospectively, I will describe what I think will be the huge contribution of this breakthrough for the future of proteomics.