Abstract
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a unique paracaspase protein whose protease activity mediates oncogenic NF-κB signalling in activated B cell-like diffuse large B cell lymphomas (ABC-DLBCLs). ABC-DLBCLs are aggressive lymphomas with high resistance to current chemotherapies. Low survival rate among patients emphasizes the urgent need for alternative treatment options. The characterization of the MALT1 will be an essential tool for developing new target-directed drugs against MALT1 dependent disorders. As the first step in the atomic-level NMR studies of the system, here we report, the 15N/13C/1H backbone assignment of the apo form of the MALT1 paracaspase region together with the third immunoglobulin-like (Ig3) domain, 44 kDa, by high resolution NMR. In addition, the non-uniform sampling (NUS) based targeted acquisition procedure is evaluated as a mean of decreasing acquisition and analysis time for larger proteins.
Highlights
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) has a central role in transcription factor NF-κB signalling [1, 2]
The 1H, 13C and 15N backbone chemical shifts were referred to DSS-d6, 13C and 15N chemical shifts were referred indirectly, and have been deposited in the Biological Magnetic Resonance Data Bank [27] with the BMRB accession code 25674
In this work we present the NMR backbone assignment of apo MALT1Casp-Ig3 in solution and show that the secondary structure deduced from the chemical shifts resemble the secondary structure observed in the apo X-ray structures
Summary
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) has a central role in transcription factor NF-κB signalling [1, 2]. NF-κB controls the expression of numerous anti-apoptotic and proliferation-promoting genes and has a key role in B-cell activation. Constitutive MALT1 activity is one characteristic of specific types of B-cell lymphomas [3, 4], rendering MALT1 as a potential drug target for these malignancies. Upon antigen stimulation MALT1 acts as a scaffold for a protein complex formed with CARMA1 and Bcl, the CBM complex [5]. The complex mediates the further events that lead to the nuclear translocation and activation of NF-κB. MALT1 functions as a protease that acts on several proteins involved in the pathway leading to NF-κB activation [6, 7]
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