{"doi":"10.1101/2024.02.01.578365","title":"Towards understanding of allostery in MALT1: a possible role of interdomain motions as revealed by NMR and AlphaFold","abstract":"ABSTRACT Mucosa-associated lymphoid tissue lymphoma-translocation protein 1 (MALT1) has emerged as an attractive target for the development of modulatory compounds, particularly in the treatment of lymphoma and other cancers. While the three-dimensional structure of MALT1(PCASP-Ig3) 339–719 has been previously determined through X-ray analysis, its dynamic behaviour in solution has remained largely unexplored. We present here inaugural dynamic analyses of the apo MALT1(PCASP-Ig3) 339–719 form along with its mutated variant, E549A. This investigation harnessed an array of NMR relaxation techniques, including longitudinal and transverse 15 N auto-relaxation, heteronuclear NOE, transverse cross-correlated relaxation and NOE measurements between side-chain methyl groups. Our findings unequivocally confirm that MALT1(PCASP-Ig3) 339–719 exists solely as a monomer in solution, and demonstrate that the two domains display semi-independent movements in relation to each other. Our extensive dynamic study, covering a range of time scales, along with the assessment of diverse conformational populations for MALT1(PCASP-Ig3) 339–719 , by Molecular Dynamic simulations, Alpha Fold modelling and PCA analysis, shed light at potential mechanisms underlying the allosteric regulation of this enzyme, and the specific importance of interdomain motions.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":493883,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9598,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":424998,"name":"Xiao Han","orcid":"0000-0003-0879-4119","position":1,"is_corresponding":false},{"id":1256593,"name":"Maria Levkovets","orcid":"0000-0002-1805-9057","position":2,"is_corresponding":false},{"id":893175,"name":"Dmitry Lesovoy","orcid":"0000-0002-9130-715X","position":3,"is_corresponding":false},{"id":1256594,"name":"Daniel Malmodin","orcid":"0000-0001-8528-0141","position":4,"is_corresponding":false},{"id":1256595,"name":"Claudio Mirabello","orcid":"0000-0001-7868-034X","position":5,"is_corresponding":false},{"id":1232622,"name":"Björn Wallner","orcid":"0000-0002-3772-8279","position":6,"is_corresponding":false},{"id":424997,"name":"Renhua Sun","orcid":"0000-0002-8203-4946","position":7,"is_corresponding":false},{"id":1088560,"name":"Tatyana Sandalova","orcid":"0000-0002-7694-6420","position":8,"is_corresponding":false},{"id":893176,"name":"Peter Agback","orcid":"0000-0003-2226-0746","position":9,"is_corresponding":false},{"id":1250891,"name":"Göran Karlsson","orcid":"0000-0002-1821-4715","position":10,"is_corresponding":false},{"id":424999,"name":"Adnane Achour","orcid":"0000-0003-0432-710X","position":11,"is_corresponding":false},{"id":821232,"name":"P. Agback","orcid":"0000-0003-1325-6024","position":12,"is_corresponding":false},{"id":239578,"name":"Vladislav Orekhov","orcid":"0000-0002-7892-6896","position":13,"is_corresponding":false},{"id":1256592,"name":"Johan Wallerstein","orcid":"0009-0005-9832-5210","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T02:09:07.920649Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}