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Shape changes induced by N-terminal platination of ubiquitin by cisplatin
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Williams, Jonathan P., Phillips, Hazel I. A., Campuzano, Iain and Sadler, P. J. (2010) Shape changes induced by N-terminal platination of ubiquitin by cisplatin. Journal of The American Society for Mass Spectrometry, Vol.21 (No.7). pp. 1097-1106. doi:10.1016/j.jasms.2010.02.012
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Official URL: http://dx.doi.org/10.1016/j.jasms.2010.02.012
Abstract
The three-dimensional conformation of a protein is an important property and plays a key role in its biological activity. We show here that ion mobility-mass spectrometry (IM-MS) can be used to detect conformational changes in the protein ubiquitin in the gas phase induced by reaction with the anticancer drug cisplatin. The primary adduct was ubiquitin-{Pt(NH3)(2)} under denaturing conditions. Up to three different conformations appear to be generated upon platination depending on the charge state. The collision cross-sections (Omega) for each conformation indicate that the conformations of the platinated protein are contracted in size compared with unmodified ubiquitin with generally smaller Omega values. Ion mobility-tandem MS allowed determination of the platinum binding site without a requirement for prior chromatographic separation. A rapid 30-min digestion of cisplatin-modified ubiquitin with trypsin allowed the platination site to be identified as the N-terminal methionine following low-energy collision-induced dissociation (CID) studies of the modified peptide. The data were generated using a Traveling-Wave based ion mobility-MS approach. Such cisplatin-induced shape changes may have a significant effect on its function in vivo. This work highlights the usefulness of the ion-mobility mass spectrometry technique for shedding new light on such protein interactions. (J Am Soc Mass Spectrom 2010, 21, 1097-1106) (C) 2010 Published by Elsevier Inc. on behalf of American Society for Mass Spectrometry
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QC Physics Q Science > QD Chemistry Q Science > QP Physiology |
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| Divisions: | Faculty of Science > Chemistry | ||||
| Library of Congress Subject Headings (LCSH): | Cisplatin, Ubiquitin, Mass spectroscopy, Ion mobility spectroscopy, Cross sections (Nuclear physics) | ||||
| Journal or Publication Title: | Journal of The American Society for Mass Spectrometry | ||||
| Publisher: | Springer New York LLC | ||||
| ISSN: | 1044-0305 | ||||
| Official Date: | July 2010 | ||||
| Dates: |
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| Volume: | Vol.21 | ||||
| Number: | No.7 | ||||
| Number of Pages: | 10 | ||||
| Page Range: | pp. 1097-1106 | ||||
| DOI: | 10.1016/j.jasms.2010.02.012 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | University of Warwick Research Development Fund, Engineering and Physical Sciences Research Council (EPSRC), University of Warwick |
Data sourced from Thomson Reuters' Web of Knowledge
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