Assignment of IVL-Methyl side chain of the ligand-free monomeric human MALT1 paracaspase-IgL 3 domain in solution

Abstract

Mucosa-associated lymphoid tissue protein 1 (MALT1) plays a key role in adaptive immune responses by modulating specific intracellular signalling pathways that control the development and proliferation of both T and B cells. Dysfunction of these pathways is coupled to the progress of highly aggressive lymphoma as well as to potential development of an array of different immune disorders. In contrast to other signalling mediators, MALT1 is not only activated through the formation of the CBM complex together with the proteins CARMA1 and Bcl10, but also by acting as a protease that cleaves multiple substrates to promote lymphocyte proliferation and survival via the NF-κB signalling pathway. Herein, we present the partial 1H, 13C Ile/Val/Leu-Methyl resonance assignment of the monomeric apo form of the paracaspase-IgL3 domain of human MALT1. Our results provide a solid ground for future elucidation of both the three-dimensional structure and the dynamics of MALT1, key for adequate development of inhibitors, and a thorough molecular understanding of its function(s).

NMR spectrum reconstruction as a pattern recognition problem

“…For the NMR experiments, we used the previously described protein samples: U -15 N- 13 C -labeled Cu(I) azurin (14 kDa) [42], U -15 N-13 C -labeled ubiquitin (8.6 kDa) [43], and U -15 -N-13 C-2 H methyl ILV back-protonated MALT1 (44 kDa) [31,32]. The fully sampled two-dimensional experiments used in this study are described in Table 4.…”

“…the same NUS schedule for all training spectra, WNN-P and WNN-R trained on different NUS tables from Poisson-gap and flat-random distribution, respectively. Finally, as another demonstration of the pattern recognition by WNN, we present the virtual decoupling on the example of a methyl 1 H- 13 C -HMQC spectrum in the 44 kDa protein MALT1 [31,32].…”

NMR spectrum reconstruction as a pattern recognition problem

“…For the NMR experiments, we used the previously described protein samples: U -15 N-13 C -labeled Cu(I) azurin (14 kDa) [40], U -15 N-13 C -labeled ubiquitin (8.6 kDa) [41], and U -15 N-13 C-2 H methyl ILV backprotonated MALT1 (44 kDa) [30,31]. Fully sampled twodimensional experiments used in this study are described in Table 4.…”

“…the same, NUS schedule for all training spectra, WNN-P and WNN-R trained on different NUS tables from Poisson-gap and flat-random distribution, respectively. Finely, as another demonstration of the pattern recognition by WNN, we present the virtual decoupling on the example of a methyl 1 H- 13 C -HMQC spectrum in the 44 kDa protein MALT1 [30,31].…”