研究领域

Physical and Theoretical Chemistry

We are interested in all aspects of protein complexes and their properties in the gas phase of a mass spectrometer. Although not the traditional role of this analytical tool, recent developments enable mass spectrometry to probe large intact protein assemblies, providing knowledge of their stoichiometry, topology and interaction partners. I have chosen to highlight two research areas here: 3D models of protein complexes Knowledge of the masses of protein assemblies is only one part of the mass spectrometry experiment. Disruption of protein complexes in solution and gas phases is leading to subunit interaction maps and architectural models (1). Such models are enhanced by shape information that can be gleaned through coupling with ion mobility mass spectrometry, in which the collision cross-section of a protein complex can be defined (2). Linking these attributes with knowledge of subunit dynamics and the role of post-translational modifications on the stability and interactions within complexes is increasing our understanding of the factors that stabilise and convert protein complexes between different quaternary states (3). Study of membrane protein complexes Membrane protein complexes are notoriously difficult to study, particularly those that contain both membrane and soluble protein subunits since in order to maintain solubility, large quantities of detergent are required. Recently we showed however that these complexes, when introduced in detergent micelles, can be liberated from the electrospray droplet (4). Once in the gas phase, activation of the protein micelle complex yields the largely detergent free complex, enabling accurate mass measurement to reveal subunit stoichiometry, lipid interactions and small molecule binding. Recently we have shown that such approaches can be applied intact ATP synthases (5). These large molecular motors can survive intact in the gas phase of a mass spectrometer enabling us to reveal the consequences of lipid and nucleotide binding on their structure and function.

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C. Bechara, A. Nöll, N. Morgne, M. T. Degiacomi R. Tampé and C. V. Robinson A subset of annular lipids is linked to the flippase activity of an ABC transporter. Nat Chem 2015, 7(3), 255-262 M. Landreh and C. V. Robinson A new window into the molecular physiology of membrane proteins. J. Physiol 2015,593(2), 355-362 S. Mehmood, T. M. Allison and C. V. Robinson Mass spectrometry of protein complexes: From origins to applications Annu Rev Phys Chem 2015, in press T. Ochi, A. N. Blackford, J. Coates, S. Jhujh, S. Mehmood, N. Tamura, J. Travers, Q. Wu, V. M. Draviam, C. V. Robinson, T. L. Blundell and S. P. Jackson DNA repair. PAXX, a paralog of XRCC4 and XLF, interacts with Ku to promote DNA double-strand break repair Science (New York, N.Y.), 2015, 347(6218), 185-188 S. Trowitzsch, C., Viola, E. Scheer, S. Conic, V. Chavant, M. Fournier, G. Papai, I. O. Ebong, C. Schaffitzel, J. Zou, M. Haffke, J. Rappsilber, C. V. Robinson, P. Schultz, L. Tora and I. Berger Cytoplasmic TAF2-TAF8-TAF10 complex provides evidence for nuclear holo-TFIID assembly from preformed submodules Nat Commun 2015, 6, 6011 A. Politis, C. Schmidt, E. Tjioe, A. M. Sandercock, K. Lasker, Y. Gordiyenko, D. Russel, A. Sali and C. V. Robinson Topological models of heteromeric protein assemblies from mass spectrometry: Application to the yeas elF3:elF5 complex. Chem Biol 2015, 22(1), 117-128 L. Wawiórka, D. Krokowski, Y. Gordienko, D. Krowarsch, C. V. Robinson, I. Adam, N. Grankowski and M. Tchórzewski In vivo formation of Plasmodium falciparum ribosomal stalk – a unique mode of assembly without stable heterodimeric intermediates. Biochimica et Biophysica Acta 2015, 1850(1), 150-158 L. A. Nematollahi, A. Garza-Garcia, C. Bechara, D. Esposito, N. Morgner, C. V. Robinson and P. C. Driscoll Flexible stoichiometry and asymmetry of the PIDDosome core complex by heteronuclear NMR spectroscopy and mass spectrometry. J Mol Biol 2015, in press