{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["21"],"submitter":["Polyansky AA"],"pubmed_abstract":["Constitutive activation of receptor tyrosine kinases (RTKs) via different mutations has a strong impact on the development of severe human disorders, including cancer. Here we propose a putative activation scenario of RTKs, whereby transmembrane (TM) mutations can also promote higher-order oligomerization of the receptors that leads to the subsequent ligand-free activation. We illustrate this scenario using a computational modelling framework comprising sequence-based structure prediction and all-atom 1 µs molecular dynamics (MD) simulations in a lipid membrane for a previously characterised oncogenic TM mutation V536E in platelet-derived growth factor receptor alpha (PDGFRA). We show that in the course of MD simulations the mutant TM tetramer retains stable and compact configuration stren"],"journal":["Computational and structural biotechnology journal"],"pagination":["2837-2844"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10192832"],"repository":["biostudies-literature"],"pubmed_title":["On a mechanistic impact of transmembrane tetramerization in the pathological activation of RTKs."],"pmcid":["PMC10192832"],"pubmed_authors":["Polyansky AA","Efremov RG"],"additional_accession":[]},"is_claimable":false,"name":"On a mechanistic impact of transmembrane tetramerization in the pathological activation of RTKs.","description":"Constitutive activation of receptor tyrosine kinases (RTKs) via different mutations has a strong impact on the development of severe human disorders, including cancer. Here we propose a putative activation scenario of RTKs, whereby transmembrane (TM) mutations can also promote higher-order oligomerization of the receptors that leads to the subsequent ligand-free activation. We illustrate this scenario using a computational modelling framework comprising sequence-based structure prediction and all-atom 1 µs molecular dynamics (MD) simulations in a lipid membrane for a previously characterised oncogenic TM mutation V536E in platelet-derived growth factor receptor alpha (PDGFRA). We show that in the course of MD simulations the mutant TM tetramer retains stable and compact configuration stren","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023","modification":"2026-05-29T02:18:44.465Z","creation":"2025-02-19T02:23:01.861Z"},"accession":"S-EPMC10192832","cross_references":{"pubmed":["37216019"],"doi":["10.1016/j.csbj.2023.04.021"]}}