Assignment of heteronuclear methyl-NMR spectrum of the 44 kDa protein MALT1 Casp-IgL3

Abstract: Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) plays an important role in the immune pathway that controls the activation and proliferation of B and T cells. Dysregularization of this pathway leads to the development of highly aggressive lymphomas. The proteolytic activity of MALT1 can be pharmacologically regulated making this protein an attractive anti-cancer drug target. In this thesis, I study two domains of MALT1 (Casp and IgL3) responsible for its proteolytic activity with nuclear magnetic resonance spectroscopy (NMR). I perform the 1H, 13C Ile, Val, Leu-methyl assignment of monomeric MALT1 Casp-IgL3 domains using methyl out-and-back experiments based on the existing backbone assignment and the information from the protein structure. The protein structures that were used for this thesis are the x-ray dimer structure of MALT1, and the structure predicted by the AlphaFold protein prediction software. I have compared AlphaFold structures with the x-ray structure. The methyl assignment that I have performed provides an opportunity for further studies of monomeric MALT1 structure and dynamics which is the key to anti-cancer drug design.