The Role of Electron Transfer Dissociation in Modern Proteomics

Nicholas M. Riley†,‡ and Joshua J. Coon*,†,‡,§,∥ †Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States ‡Genome Center of Wisconsin, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, United States Morgridge Institute for Research, Madison, Wisconsin 53715, United States ■ CONTENTS Principles of ETD 40 Supplemental Activation for ETD Reactions 41 ETD-Equipped Instrumentation 42 ETD and Top-Down Proteomics 44 Characterizing Post-Translational Modifications with ETD 46 Phosphorylation 46 Glycosylation 46 Disulfide Bonds 48 Alternative Proteases, Middle-Down Proteomics, and Peptidomics 49 Cases Where ETD is Particularly Helpful 50 Major Histocompatibility Complex/Human Leukocyte Antigen Peptides 50 Histones 50 Antibody Characterization 51 Structural Characterization Using ETD 51 Cross-Linked Peptides 51 Ion Mobility and Native Proteomics 52 Hydrogen−Deuterium Exchange 52 Other Uses of ETD and Related Ion−Ion Reactions 53 Proton Transfer and Other Ion−Ion Reactions 54 Negative Electron Transfer Dissociation 54 Quantitative Proteomic Strategies 55 New Informatic Tools for ETD and Related Technologies 56 Looking Forward 57 Author Information 57 Corresponding Author 57 ORCID 57 Notes 57 Biographies 57 Acknowledgments 57 References 57