Dataset Information

Assignment of IVL-Methyl side chain of the ligand-free monomeric human MALT1 paracaspase-IgL₃ 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).

SUBMITTER: Han X

PROVIDER: S-EPMC9510110 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Assignment of IVL-Methyl side chain of the ligand-free monomeric human MALT1 paracaspase-IgL<sub>3</sub> domain in solution.

Han Xiao X Levkovets Maria M Lesovoy Dmitry D Sun Renhua R Wallerstein Johan J Sandalova Tatyana T Agback Tatiana T Achour Adnane A Agback Peter P Orekhov Vladislav Yu VY

Biomolecular NMR assignments 20220912 2

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 compl ...[more]

PMID: 36094731

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Project description:One bottleneck in NMR structure determination lies in the laborious and time-consuming process of side-chain resonance and NOE assignments. Compared to the well-studied backbone resonance assignment problem, automated side-chain resonance and NOE assignments are relatively less explored. Most NOE assignment algorithms require nearly complete side-chain resonance assignments from a series of through-bond experiments such as HCCH-TOCSY or HCCCONH. Unfortunately, these TOCSY experiments perform poorly on large proteins. To overcome this deficiency, we present a novel algorithm, called NASCA: (NOE Assignment and Side-Chain Assignment), to automate both side-chain resonance and NOE assignments and to perform high-resolution protein structure determination in the absence of any explicit through-bond experiment to facilitate side-chain resonance assignment, such as HCCH-TOCSY. After casting the assignment problem into a Markov Random Field (MRF), NASCA: extends and applies combinatorial protein design algorithms to compute optimal assignments that best interpret the NMR data. The MRF captures the contact map information of the protein derived from NOESY spectra, exploits the backbone structural information determined by RDCs, and considers all possible side-chain rotamers. The complexity of the combinatorial search is reduced by using a dead-end elimination (DEE) algorithm, which prunes side-chain resonance assignments that are provably not part of the optimal solution. Then an A* search algorithm is employed to find a set of optimal side-chain resonance assignments that best fit the NMR data. These side-chain resonance assignments are then used to resolve the NOE assignment ambiguity and compute high-resolution protein structures. Tests on five proteins show that NASCA: assigns resonances for more than 90% of side-chain protons, and achieves about 80% correct assignments. The final structures computed using the NOE distance restraints assigned by NASCA: have backbone RMSD 0.8-1.5 Å from the reference structures determined by traditional NMR approaches.

Dataset Information

Assignment of IVL-Methyl side chain of the ligand-free monomeric human MALT1 paracaspase-IgL₃ domain in solution.

Publications

Assignment of IVL-Methyl side chain of the ligand-free monomeric human MALT1 paracaspase-IgL<sub>3</sub> domain in solution.

Similar Datasets

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Dataset Information

Assignment of IVL-Methyl side chain of the ligand-free monomeric human MALT1 paracaspase-IgL3 domain in solution.

Publications

Assignment of IVL-Methyl side chain of the ligand-free monomeric human MALT1 paracaspase-IgL<sub>3</sub> domain in solution.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Assignment of IVL-Methyl side chain of the ligand-free monomeric human MALT1 paracaspase-IgL₃ domain in solution.