An integrative approach for modelling large protein complexes using mass spectrometry-based strategies and computational analyses


This is to integrate a novel combination of mass spectrometry (MS)-based experiments with protein assembly modelling and bioinformatics tools for studying the structural dynamics of transient protein complexes. Structural data generated from MS – native MS, ion mobility (IM)-MS and hydrogen deuterium exchange (HDX)-MS - will be encoded into modelling restraints and subsequently analysed by protein-protein interaction networks for building 3D protein assembly models. We will validate our method on a benchmark of heteromeric complexes with known crystal structures and use it to characterize the assembly dynamics of the recently discovered antiviral defense system, clustered regularly interspaced palindromic repeats (CRISPR) complex.


Robinson, C. V., Sali, A., and Baumeister, W. (2007) The molecular sociology of the cell, Nature 450, 973-982.


Politis, A., Stengel, F., Hall, Z., Hernandez, H., Leitner, A., Waltzhoeni, T., Robinson, C. V., and Aebersold, R. (2014) A mass spectrometry-based hybrid method for structural modelling of protein complexes, Nature Methods 11, 4.


De Simone, A., Dodson, G. G., Verma, C. S., Zagari, A., and Fraternali, F. (2005) Prion and water: tight and dynamical hydration sites have a key role in structural stability, Proceedings of the National Academy of Sciences of the United States of America 102, 7535-7540.


Chung, S. S., Pandini, A., Annibale, A., Coolen, A. C., Thomas, N. S., and Fraternali, F. (2015) Bridging topological and functional information in protein interaction networks by short loops profiling, Scientific Reports 5, 8540.


Rouillon, C., Zhou, M., Zhang, J., Politis, A., Beilsten-Edmands, V., Cannone, G., Graham, S., Robinson, C. V., Spagnolo, L., and White, M. F. (2013) Structure of the CRISPR interference complex CSM reveals key similarities with cascade, Molecular Cell 52, 124-134.

Biological Areas:

Structural Biology
Chemical Biology


Molecules, cells and industrial biotechnology