Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/105289
DC Field | Value | Language |
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dc.contributor.author | Almeida, Beatriz C. | - |
dc.contributor.author | Kaczmarek, Jennifer A. | - |
dc.contributor.author | Figueiredo, Pedro | - |
dc.contributor.author | Prather, Kristala L. J. | - |
dc.contributor.author | Carvalho, Alexandra T. P. | - |
dc.date.accessioned | 2023-02-15T09:06:17Z | - |
dc.date.available | 2023-02-15T09:06:17Z | - |
dc.date.issued | 2021-06 | - |
dc.identifier.issn | 2631-9268 | pt |
dc.identifier.uri | https://hdl.handle.net/10316/105289 | - |
dc.description.abstract | The development of new synthetic biology circuits for biotechnology and medicine requires deeper mechanistic insight into allosteric transcription factors (aTFs). Here we studied the aTF UxuR, a homodimer of two domains connected by a highly flexible linker region. To explore how ligand binding to UxuR affects protein dynamics we performed molecular dynamics simulations in the free protein, the aTF bound to the inducer D-fructuronate or the structural isomer D-glucuronate. We then validated our results by constructing a sensor plasmid for D-fructuronate in Escherichia coli and performed site-directed mutagenesis. Our results show that zinc coordination is necessary for UxuR function since mutation to alanines prevents expression de-repression by D-fructuronate. Analyzing the different complexes, we found that the disordered linker regions allow the N-terminal domains to display fast and large movements. When the inducer is bound, UxuR can sample an open conformation with a more pronounced negative charge at the surface of the N-terminal DNA binding domains. In opposition, in the free and D-glucuronate bond forms the protein samples closed conformations, with a more positive character at the surface of the DNA binding regions. These molecular insights provide a new basis to harness these systems for biological systems engineering. | pt |
dc.language.iso | eng | pt |
dc.publisher | Oxford University Press | pt |
dc.relation | MIT-Portugal seed project 6937814 | pt |
dc.relation | UIDB/04539/2020 | pt |
dc.relation | IF/01272/2015 | pt |
dc.relation | SFRH/BD/144303/2019 | pt |
dc.relation | SFRH/BD/150697/2020 | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/ | pt |
dc.title | Transcription factor allosteric regulation through substrate coordination to zinc | pt |
dc.type | article | - |
degois.publication.firstPage | lqab033 | pt |
degois.publication.issue | 2 | pt |
degois.publication.title | NAR Genomics and Bioinformatics | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1093/nargab/lqab033 | pt |
degois.publication.volume | 3 | pt |
dc.date.embargo | 2021-06-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.languageiso639-1 | en | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.grantfulltext | open | - |
item.fulltext | Com Texto completo | - |
item.cerifentitytype | Publications | - |
item.openairetype | article | - |
crisitem.project.grantno | Center for Innovative Biomedicine and Biotechnology - CIBB | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.researchunit | CNC - Center for Neuroscience and Cell Biology | - |
crisitem.author.orcid | 0000-0002-1243-0265 | - |
Appears in Collections: | I&D CNC - Artigos em Revistas Internacionais |
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File | Description | Size | Format | |
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Transcription factor allosteric regulation through substrate coordination to zinc.pdf | 6.89 MB | Adobe PDF | View/Open |
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This item is licensed under a Creative Commons License