Shape changes induced by N-terminal platination of ubiquitin by cisplatin

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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(NH 3 ) 2 } under denaturing conditions. Up to three different conformations appear to be generated upon platination depending on the charge state. The collision cross-sections (Ω) for each conformation indicate that the conformations of the platinated protein are contracted in size compared with unmodified ubiquitin with generally smaller Ω 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. © 2010.

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Williams, J. P., Phillips, H. I. A., Campuzano, I., & Sadler, P. J. (2010). Shape changes induced by N-terminal platination of ubiquitin by cisplatin. Journal of the American Society for Mass Spectrometry, 21(7), 1097–1106. https://doi.org/10.1016/j.jasms.2010.02.012

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