Agback, Peter
- Department of Molecular Sciences, Swedish University of Agricultural Sciences
Research article2024Peer reviewedOpen access
Wallerstein, Johan; Han, Xiao; Levkovets, Maria; Lesovoy, Dmitry; Malmodin, Daniel; Mirabello, Claudio; Wallner, Bjoern; Sun, Renhua; Sandalova, Tatyana; Agback, Peter; Karlsson, Goran; Achour, Adnane; Agback, Tatiana; Orekhov, Vladislav
Mucosa-associated lymphoid tissue lymphoma-translocation protein 1 (MALT1) is an attractive target for the development of modulatory compounds in the treatment of lymphoma and other cancers. While the three-dimensional structure of MALT1 has been previously determined through X-ray analysis, its dynamic behaviour in solution has remained unexplored. We present here dynamic analyses of the apo MALT1 form along with the E549A mutation. This investigation used NMR 15N relaxation and NOE measurements between side-chain methyl groups. Our findings confirm that MALT1 exists as a monomer in solution, and demonstrate that the domains display semi-independent movements in relation to each other. Our dynamic study, covering multiple time scales, along with the assessment of conformational populations by Molecular Dynamic simulations, Alpha Fold modelling and PCA analysis, put the side chain of residue W580 in an inward position, shedding light at potential mechanisms underlying the allosteric regulation of this enzyme.NMR relaxation and AlphaFold structural ensemble modelling of MALT1 reveals motions between its PCASP and Ig3 domains. This sheds light into the mechanisms of the protein's allosteric regulation.
Communications biology
2024, Volume: 7, number: 1, article number: 868Publisher: NATURE PORTFOLIO
Biochemistry and Molecular Biology
DOI: https://doi.org/10.1038/s42003-024-06558-y
https://res.slu.se/id/publ/131329