Cryo-electron tomography of HIV-1 assembly and maturation
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Retroviruses are enveloped RNA viruses, whose assembly is largely driven by the viral Gag polyprotein. Gag recruits other virion components and targets them to the viral assembly site. Oligomerization of Gag leads to formation of a protein shell at the plasma membrane and viral budding. Retroviral particles are formed in a non-infectious, immature form, containing uncleaved Gag polyproteins. To become an infectious virion, Gag must be cleaved by the viral protease (PR) at specific sites, separating functional domains and causing a rearrangement of the interior virion organization. This process is termed maturation.
We are interested in how maturation is structurally regulated, as well as how the mature Gag-derived proteins interact with the host cell during entry. In this project, you will apply cryo-electron tomography, computational image processing and other techniques to obtain structural data on HIV-1 particles and mutants at different stages of the HIV-1 lifecycle. Viruses will be studied alone and together with cells. In this way you will attempt to understand the mechanisms of maturation and the functional purpose of maturation.
This project would be best suited to someone who is interested in answering important biological questions by combining biological approaches with complex technical equipment and computational analysis.
Mattei, S., Tan, A., Glass, B., Müller, B., Kräusslich, H.-G. and Briggs, J.A.G. (2018)
High-resolution structures of HIV-1 Gag cleavage mutants determine structural switch for virus maturation.
Proceedings of the National Academy of Sciences, 115, E9401-E9410.
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.
Wan, W. and Briggs, J.A.G. (2016)
Cryo-electron tomography and subtomogram averaging (review).
Methods in Enzymology, 579, 329-367.
Mattei, S., Schur, F.K.M. and Briggs, J.A.G. (2016)
Retrovirus maturation - an extraordinary structural transformation (review).
Current Opinion in Virology, 18, 27-35.