John Briggs
Enveloped viruses and coated vesicles - electron cryo-microscopy and tomography
jbriggs@mrc-lmb.cam.ac.ukPersonal group site
We study the structure and the molecular assembly mechanisms of important, pathogenic, enveloped viruses (e.g. HIV and Influenza virus), and of cellular trafficking vesicles (e.g. clathrin and COPI coated vesicles). Viruses and vesicles are extraordinary self-assembling machines – the protein building blocks interact with one another to bring all the components or cargo together, to reshape the lipid bilayer, and to release a free virus or vesicle. The building blocks will often then undergo an intricate reassembly to prepare for fusion with a target cell or membrane. The level of understanding we aim to achieve could be imagined as a 3D, functionally annotated movie, with molecular resolution, showing the assembly and budding process.
To reach this goal we need to obtain detailed structural information at different stages during assembly, ideally under close-to-native conditions, even within cells. This is a challenge for conventional structural biology tools, so we are also developing and applying new approaches for electron cryo-microscopy and tomography, correlated fluorescence and electron microscopy, and image processing.
Selected Papers
- Peukes, J., Xiong, X., Erlendsson, S., Qu, K., Wan, W., Calder, L.J., Schraidt, O., Kummer, S., Freund, S.M.V., Kräusslich, H.G., Briggs, J.A.G. (2020)
The native structure of the assembled matrix protein 1 of influenza A virus
Nature 587(7834): 495-498. - Ke, Z., Oton, J., Qu, K., Cortese, M., Zila, V., McKeane, L., Nakane, T., Zivanov, J., Neufeldt, C.J., Cerikan, B., Lu, J.M., Peukes, J., Xiong, X., Kräusslich, H.G., Scheres, S.H.W., Bartenschlager, R., Briggs, J.A.G. (2020)
Structures and distributions of SARS-CoV-2 spike proteins on intact virions.
Nature 588(7838): 498-502. - Kovtun, O., Leneva, N., Bykov, Y.S., Ariotti, N., Teasdale, R.D., Schaffer, M., Engel, B.D., Owen, D.J., Briggs, J.A.G., Collins, B.M. (2018)
Structure of the membrane-assembled retromer coat determined by cryo-electron tomography.
Nature 561(7724): 561-564. - Wan, W., Kolesnikova, L., Clarke, M., Koehler, A., Noda, T., Becker, S., Briggs, J.A.G. (2017)
Structure and assembly of the Ebola virus nucleocapsid
Nature 551: 394-397 - Mattei, S., Glass, B., Hagen, W.J., Kräusslich, H.G. and Briggs, J.A (2016)
The structure and flexibility of conical HIV-1 capsids determined within intact virions.
Science 6318: 1434-1437 - Schur, F.K., Obr, M., Hagen, W.J., Wan, W., Jakobi, A.J., Kirkpatrick, J.M., Sachse, C., Kräusslich, H.G. and Briggs, J.A. (2016)
An atomic model of HIV-1 capsid-SP1 reveals structures regulating assembly and maturation.
Science 353(6298): 506-508 - Dodonova, S.O., Diestelkoetter-Bachert, P., von Appen, A., Hagen, W.J., Beck, R., Beck, M., Wieland, F. and Briggs, J.A. (2015)
VESICULAR TRANSPORT. A structure of the COPI coat and the role of coat proteins in membrane vesicle assembly.
Science 349(6244): 195-198 - Avinoam, O., Schorb, M., Beese, C.J., Briggs, J.A. and Kaksonen, M. (2015)
ENDOCYTOSIS. Endocytic sites mature by continuous bending and remodeling of the clathrin coat.
Science 348(6241): 1369-1372 - Schur, F.K., Hagen, W.J., Rumlová, M., Ruml, T., Müller, B., Kräusslich, H.G. and Briggs, J.A. (2015)
Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution.
Nature 517(7535): 505-508