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Native mass spectrometry: a bridge between interactomics and structural biology

Abstract

Native mass spectrometry is an emerging technology that allows the topological investigation of intact protein complexes with high sensitivity and a theoretically unrestricted mass range. This unique tool provides complementary information to established technologies in structural biology, and also provides a link to high-throughput interactomics studies, which do not generate information on exact protein complex-composition, structure or dynamics. Here I review the current state of native mass spectrometry technology and discuss several important biological applications. I also describe current experimental challenges in native mass spectrometry, encouraging readers to contribute to solutions.

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Figure 1: Denatured and native mass spectra of H. pylori urease.
Figure 2: Tandem mass spectrometry of the intact 517 kDa RNA Pol II complex.
Figure 3: The ins and outs of native mass spectrometry.
Figure 4: Native mass spectra of intact HBV viral capsids.

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Acknowledgements

I thank all colleagues in native MS who have contributed in making this area of research come to maturity. I acknowledge all members of my group, most notably the native MS (former) members whose material and input I have used here; K. Lorenzen, H. Mazon, M. Pinkse, S. Synowsky, C. Uetrecht, R. van den Heuvel, E. van Duijn and C. Versluis. K. Lorenzen and C. Uetrecht helped construct the figures. Additionally, I thank all collaborators whose samples, support and expertise have been instrumental in our work.

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Heck, A. Native mass spectrometry: a bridge between interactomics and structural biology. Nat Methods 5, 927–933 (2008). https://doi.org/10.1038/nmeth.1265

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