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. ISSN 1044-0305

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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
Subjects:	Q Science > QC Physics Q Science > QD Chemistry Q Science > QP Physiology
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
Volume:	Vol.21
Number:	No.7
Number of Pages:	10
Page Range:	pp. 1097-1106
Identification Number:	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
URI:	http://wrap.warwick.ac.uk/id/eprint/5566

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