{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["23(10)"],"submitter":["Rizza F"],"funding":["‘Consorzio Interuniversitario del Nord-Est per il Calcolo Automatico’ (CINECA) to the University of Milano-Bicocca","Italian Ministry of University and Research (MIUR)"],"pubmed_abstract":["Neurofibromin, the main RasGAP in the nervous system, is a 2818 aa protein with several poorly characterized functional domains. Mutations in the NF1-encoding gene lead to an autosomal dominant syndrome, neurofibromatosis, with an incidence of 1 out of 3000 newborns. Missense mutations spread in the Sec14-PH-encoding sequences as well. Structural data could not highlight the defect in mutant Sec14-PH functionality. By performing molecular dynamics simulations at different temperatures, we found that the lid-lock is fundamental for the structural interdependence of the NF1 bipartite Sec14-PH domain. In fact, increased flexibility in the lid-lock loop, observed for the K1750Δ mutant, leads to disconnection of the two subdomains and can affect the stability of the Sec14 subdomain."],"journal":["International journal of molecular sciences"],"pagination":["5707"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9147397"],"repository":["biostudies-literature"],"pubmed_title":["Molecular Dynamics Simulations Reveal Structural Interconnections within Sec14-PH Bipartite Domain from Human Neurofibromin."],"pmcid":["PMC9147397"],"pubmed_authors":["Vertemara J","Tisi R","Rizza F"],"additional_accession":[]},"is_claimable":false,"name":"Molecular Dynamics Simulations Reveal Structural Interconnections within Sec14-PH Bipartite Domain from Human Neurofibromin.","description":"Neurofibromin, the main RasGAP in the nervous system, is a 2818 aa protein with several poorly characterized functional domains. Mutations in the NF1-encoding gene lead to an autosomal dominant syndrome, neurofibromatosis, with an incidence of 1 out of 3000 newborns. Missense mutations spread in the Sec14-PH-encoding sequences as well. Structural data could not highlight the defect in mutant Sec14-PH functionality. By performing molecular dynamics simulations at different temperatures, we found that the lid-lock is fundamental for the structural interdependence of the NF1 bipartite Sec14-PH domain. In fact, increased flexibility in the lid-lock loop, observed for the K1750Δ mutant, leads to disconnection of the two subdomains and can affect the stability of the Sec14 subdomain.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2026-05-06T03:18:09.034Z","creation":"2025-04-05T20:39:32.399Z"},"accession":"S-EPMC9147397","cross_references":{"pubmed":["35628517"],"doi":["10.3390/ijms23105707"]}}