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Does deamidation cause protein unfolding? A top-down tandem mass spectrometry study
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Soulby, Andrew J., Heal, Jack W., Barrow, Mark P., Römer, Rudolf A. and O'Connor, Peter B. (2015) Does deamidation cause protein unfolding? A top-down tandem mass spectrometry study. Protein Science, 24 (5). pp. 850-860. doi:10.1002/pro.2659 ISSN 0961-8368.
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Official URL: http://dx.doi.org/10.1002/pro.2659
Abstract
Deamidation is a nonenzymatic post‐translational modification of asparagine to aspartic acid or glutamine to glutamic acid, converting an uncharged amino acid to a negatively charged residue. It is plausible that deamidation of asparagine and glutamine residues would result in disruption of a proteins' hydrogen bonding network and thus lead to protein unfolding. To test this hypothesis Calmodulin and B2M were deamidated and analyzed using tandem mass spectrometry on a Fourier transform ion cyclotron resonance mass spectrometer (FTICR‐MS). The gas phase hydrogen bonding networks of deamidated and nondeamidated protein isoforms were probed by varying the infra‐red multi‐photon dissociation laser power in a linear fashion and plotting the resulting electron capture dissociation fragment intensities as a melting curve at each amino acid residue. Analysis of the unfolding maps highlighted increased fragmentation at lower laser powers localized around heavily deamidated regions of the proteins. In addition fragment intensities were decreased across the rest of the proteins which we propose is because of the formation of salt‐bridges strengthening the intramolecular interactions of the central regions. These results were supported by a computational flexibility analysis of the mutant and unmodified proteins, which would suggest that deamidation can affect the global structure of a protein via modification of the hydrogen bonding network near the deamidation site and that top down FTICR‐MS is an appropriate technique for studying protein folding.
Item Type: | Journal Article | ||||||
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Chemistry Faculty of Science, Engineering and Medicine > Science > Physics |
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Journal or Publication Title: | Protein Science | ||||||
Publisher: | John Wiley & Sons Ltd. | ||||||
ISSN: | 0961-8368 | ||||||
Official Date: | 4 February 2015 | ||||||
Dates: |
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Volume: | 24 | ||||||
Number: | 5 | ||||||
Page Range: | pp. 850-860 | ||||||
DOI: | 10.1002/pro.2659 | ||||||
Status: | Peer Reviewed | ||||||
Publication Status: | Published | ||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||
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