Zanetti, Giulia - Birkbeck, University of London - Department of Biological Sciences

研究领域

The Extracellular Matrix (ECM) is a fundamental physiological component of all connective tissues in higher eukaryotes, and defects in ECM are linked to many pathological conditions. The ECM forms through the tightly controlled and regulated secretion of specialised molecules, which starts with their exit from the ER in membrane vesicles formed by the coat protein complex II (COPII). Collagens are a major component of the ECM, yet secretion of collagen precursor molecules (procollagen) poses a major challenge for the COPII trafficking machinery, as procollagen assembles in the ER into structures that are much larger than a typical COPII carrier. COPII must drive the formation of “megacarriers”, able to transport procollagen; whilst we are starting to understand how COPII coat flexibility is achieved structurally, the events and factors that drive and regulate the process of megacarrier formation remain largely unknown. I use biochemical methods and cryo-electron microscopy (cryo-tomography, subtomogram averaging and single particle reconstruction) to understand the interaction of the COPII coat complex with proteins involved in the ER exit of procollagens, such as TANGO1 and Sedlin, aiming to reveal the molecular basis for exit of procollagen from the ER.

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Zanetti, G., Prinz, S., Daum, S., Meister, A., Schekman, R., Bacia, K., and Briggs, J.A. (2013). The structure of the COPII transport-vesicle coat assembled on membranes. eLife 2, e00951. Zanetti, G., Pahuja, K.B., Studer, S., Shim, S., and Schekman, R. (2012). COPII and the regulation of protein sorting in mammals. Nature cell biology 14, 20-28. Zanetti, G., Riches, J.D., Fuller, S.D., and Briggs, J.A. (2009). Contrast transfer function correction applied to cryo-electron tomography and sub-tomogram averaging. Journal of structural biology 168, 305-312. Guo, Y., Zanetti, G., and Schekman, R. (2013). A novel GTP-binding protein-adaptor protein complex responsible for export of Vangl2 from the trans Golgi network. eLife 2, e00160. Briggs, J.A., Riches, J.D., Glass, B., Bartonova, V., Zanetti, G., and Krausslich, H.G. (2009). Structure and assembly of immature HIV. Proceedings of the National Academy of Sciences of the United States of America 106, 11090-11095. Zanetti, G., Briggs, J.A., Grunewald, K., Sattentau, Q.J., and Fuller, S.D. (2006). Cryo-electron tomographic structure of an immunodeficiency virus envelope complex in situ. PLoS pathogens 2, e83. Sasson, S.C., Zaunders, J.J., Zanetti, G., King, E.M., Merlin, K.M., Smith, D.E., Stanley, K.K., Cooper, D.A., and Kelleher, A.D. (2006). Increased plasma interleukin-7 level correlates with decreased CD127 and Increased CD132 extracellular expression on T cell subsets in patients with HIV-1 infection. The Journal of infectious diseases 193, 505-514. Staunton, D., Schlinkert, R., Zanetti, G., Colebrook, S.A., and Campbell, I.D. (2006). Cell-free expression and selective isotope labelling in protein NMR. Magnetic resonance in chemistry : MRC 44 Spec No, S2-9. van Thor, J.J., Zanetti, G., Ronayne, K.L., and Towrie, M. (2005). Structural events in the photocycle of green fluorescent protein. The journal of physical chemistry B 109, 16099-16108.