Restraining expansion of the peak envelope in H/D exchange-MS and its application in detecting perturbations of protein structure/dynamics

Analytical Chemistry
Gordon W SlyszDavid C Schriemer

Abstract

Hydrogen/deuterium exchange (H/DX) mass spectrometry (MS) is increasingly applied to problems in protein structural biology in order to map protein dynamics and identify sites of interactions. In theory, an MS-based readout of deuterium label incorporation can overcome the concentration, size, purity, and complexity limitations inherent in NMR-based measurements of exchange; however, in practice, these advantages are reduced due to spectral interference and dilution of the sample in deuterium oxide (D 2O). In this study, we demonstrate that popular H/DX labeling strategies aggravate the interference problem and that significant recovery of spectral capacity may be achieved with a "minimalist" strategy. Simulations of peptide deuteration justify large reductions in the level of D 2O used in labeling experiments, as well as reduced numbers of peaks used in making relative labeling measurements between biochemical states of a protein. To demonstrate the utility of a minimalist approach, calmodulin was interrogated in a bottom-up H/DX-MS workflow, and sensitivity to the addition of Ca (2+) as a structural perturbation was measured as a function of % D 2O and the number of peaks used in quantitating deuteration level. It is shown th...Continue Reading

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Citations

Sep 11, 2013·Journal of the American Society for Mass Spectrometry·Miklos GuttmanKelly K Lee
Apr 14, 2011·The Journal of Biological Chemistry·Leslie P SilvaDavid C Schriemer
Dec 1, 2012·Molecular & Cellular Proteomics : MCP·Kyle M BurnsDavid C Schriemer
May 29, 2009·BMC Bioinformatics·Gordon W SlyszDavid C Schriemer
Nov 3, 2012·Biochimica Et Biophysica Acta·Sheila S Jaswal
May 5, 2012·Protein Expression and Purification·Ansgar Brock
Aug 13, 2009·Mass Spectrometry Reviews·Lars KonermannXin Tong
May 27, 2015·Protein Science : a Publication of the Protein Society·Kyle M BurnsDavid C Schriemer
Nov 27, 2014·Analytical Chemistry·Joey G Sheff, David C Schriemer
Jan 29, 2014·Journal of Proteome Research·Gordon W SlyszMary S Lipton
Dec 22, 2010·Chemical Society Reviews·Lars KonermannYu-Hong Liu
Jul 28, 2020·Biomedicines·Dominic NarangDerek J Wilson
Jun 2, 2020·Journal of Proteomics·Daniel S ZiemianowiczDavid C Schriemer
Aug 18, 2009·Analytical Chemistry·Andrew J PercyDavid C Schriemer

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