Differentially modified proteins (proteoforms) can differ significantly in their biological activity. Proteoforms originate from the same gene but differ in their amino acid sequences and/or post-translational modifications. Because function of a protein is often intimately linked to its structural heterogeneity, a key question is thus to identify how proteoform variants differ in their structural heterogeneity.<br/><br/>This contribution will discuss progress made in my lab towards experimental and computational ion mobility spectrometry – mass spectrometry methods and how these methods offer the potential to reveal how sequence and post-translational modifications of a proteoform regulate its structural heterogeneity.<br/><br/>Specifically, we will discuss our newly-developed tandem-trapped ion mobility spectrometry – mass spectrometry (TIMS/TIMS-MS) instrument and its ability to characterize structure and sequence of proteins and protein complexes. We will also discuss how ion mobility spectra can be quantitative interpreted in term of the ion structure and how these methods are used to reveal which aspects of the native structure of a protein are retained in the gas phase, for how long, and under which conditions. Case studies include the proteins ubiquitin, alpha-synuclein, CCL5/RANTES, and the tetrameric protein complex avidin.

Tandem-trapped ion mobility spectrometry / mass spectrometry for structural biology applications

2019 Spring National Meeting

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