Electrospray mass spectrometry can provide detailed insights into protein structures, dynamics, and interactions. Key to the feasibility of such experiments is the transfer of proteins and peptides from solution into the gas phase. This talk will start by highlighting recent experimental and computational work on the mechanisms of these electrospray events. We will then proceed to discuss hydrogen/deuterium exchange techniques that can decipher the inner workings of soluble and membrane-bound proteins. We will illustrate this approach in experiments on ATP synthase, the world’s smallest rotational motor. By combining mass spectrometry experiments with molecular dynamics simulations, we were able to uncover previously unknown aspects of this motor protein. Another focus will be our work towards a thermodynamic framework for modeling temperature-dependent hydrogen exchange data, an approach that can map protein energy landscapes. We will also discuss recent work on the peroxidase activation mechanism of cytochrome c which is closely related to the mechanism of apoptosis.
Lars Konermann is Professor of Chemistry at The University of Western Ontario in London, ON, Canada, with a cross-appointment in the Biochemistry Department. Konermann did his Ph.D. work at the Max-Planck-Institute in Mulheim/Germany (1993-1996). After a post-doctoral fellowship at the University of British Columbia/Canada (1996-1998) he moved to his current position at Western. Research in Konermann's laboratory focuses on biophysical and bioanalytical protein chemistry. Many of his projects involve the development and application of new mass spectrometry techniques and computational tools. Konermann is the recipient of the Canadian Society for Chemistry (CSC) Aroca Award, CSC McBryde Medal, CSC Beamish Award, UWO Bucke Science Prize, UWO Faculty Scholar Award, ETP Ken Standing Award, and CSMS Lossing Award. In 2015 he was named Distinguished Research Professor, and from 2004 to 2014 he held a Canada Research Chair. In 2018 he was elected as a Fellow of the Royal Society of Canada (FRSC). Konermann also received a number of undergraduate teaching awards, and he serves as Chair of the Lake Louise Tandem Mass Spectrometry Workshop (www.lakelouisemsms.org).
"Interrogating the Quaternary Structure of Noncanonical Hemoglobin Complexes by Electrospray Mass Spectrometry and Collision-Induced Dissociation" A. I. M. Sever, V. Yin, and L. Konermann J. Am. Soc. Mass Spectrom., 32, 270 (2021).
"Formation of Gaseous Proteins via the Ion Evaporation Model (IEM) in Electrospray Mass Spectrometry" E. Aliyari and L. Konermann Anal. Chem. 92, 10807 (2020).
"Analysis of Temperature-Dependent H/D Exchange Mass Spectrometry Experiments" N. N. Tajoddin and L. Konermann Anal. Chem. 92, 10058 (2020).
"Lysine Carbonylation is a Previously Unrecognized Contributor to Peroxidase Activation of Cytochrome c by Chloramine-T" V. Yin, S. Mian, and L. Konermann Chem. Sci. 10, 2349 (2019).
"Charging and Supercharging of Proteins for Mass Spectrometry: Recent Insights into the Mechanisms of Electrospray Ionization" L. Konermann, H. Metwally, Q. Duez, and I. Peters Analyst 144, 6157 (2019).
"Evidence for a Partially Stalled γ Rotor in F1-ATPase from H/D Exchange Experiments and Molecular Dynamics Simulations" A. Murcia Rios, S. Vahidi, S. D. Dunn, and L. Konermann JACS 140, 14860 (2018).
"Calcium-Mediated Control of S100 Proteins: Allosteric Communication via an Agitator/Signal Blocking Mechanism" Y. Xiao, G. S. Shaw, and L. Konermann JACS 139, 11460 (2017).
"Load-dependent destabilization of the gamma-rotor shaft in FOF1 ATP synthase revealed by H/D-exchange mass spectrometry" S. Vahidi, Y. Bi, S. D. Dunn, and L. Konermann PNAS 113, 2412 (2016).