Abstract
Mind Bomb 1 (MIB1) is a large multi domain ubiquitin ligase which controls crucial cellular pathways such as Notch signal transduction, centriolar organisation and apoptotic signalling. Its prevalent role in regulating multiple cellular processes is substantiated by the fact that MIB1 is a critical target during the viral infection of different species including adenoviruses, Zika virus and coronavirus. This project aims to elucidate the structural basis of the ubiquitin transfer mechanism catalysed by Mind Bomb ubiquitin ligases. Using an interdisciplinary approach of structural biology, physical biochemistry and chemical biology we will determine how virus-host interactions manipulate this process.
References
1 Specificity in Ubiquitination Triggered by Virus Infection. Gu H, et al.
Int J Mol Sci. 2020 Jun 8;21(11)
2 Structure and function of the Mind bomb E3 ligase in the context of Notch signal transduction.
Guo B, et al. Curr Opin Struct Biol. 2016 Dec;41:38-45
3 The E3 Ubiquitin Ligase Mind Bomb 1 Controls Adenovirus Genome Release at the Nuclear Pore Complex. Bauer M et al. Cell Rep. 2019 Dec 17;29(12):3785-3795.
4 Zika virus increases mind bomb 1 levels, causing degradation of pericentriolar material 1 (PCM1) and dispersion of PCM1-containing granules from the centrosome.
Wen F, et al. J Biol Chem. 2019 Dec 6;294(49):18742-18755
5 A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Gordon DE, et al. Nature. 2020 Apr 30. doi: 10.1038/s41586-020-2286-9.