Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/109924
DC Field | Value | Language |
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dc.contributor.author | Harley, Carol A. | - |
dc.contributor.author | Jesus, Catarina S. H. | - |
dc.contributor.author | Carvalho, Ricardo | - |
dc.contributor.author | Brito, Rui M. M. | - |
dc.contributor.author | Morais-Cabral, João H. | - |
dc.date.accessioned | 2023-11-07T10:58:04Z | - |
dc.date.available | 2023-11-07T10:58:04Z | - |
dc.date.issued | 2012 | - |
dc.identifier.issn | 1932-6203 | pt |
dc.identifier.uri | http://hdl.handle.net/10316/109924 | - |
dc.description.abstract | Inherited human long-QT2 syndrome (LQTS) results from mutations in the gene encoding the HERG channel. Several LQT2-associated mutations have been mapped to the amino terminal cytoplasmic Per-Arnt-Sim (PAS) domain of the HERG1a channel subunit. Here we have characterized the trafficking properties of some LQT2-associated PAS domain mutants and analyzed rescue of the trafficking mutants by low temperature (27°C) or by the pore blocker drug E4031. We show that the LQT2-associated mutations in the PAS domain of the HERG channel display molecular properties that are distinct from the properties of LQT2-associated mutations in the trans-membrane region. Unlike the latter, many of the tested PAS domain LQT2-associated mutations do not result in trafficking deficiency of the channel. Moreover, the majority of the PAS domain mutations that cause trafficking deficiencies are not rescued by a pore blocking drug. We have also explored the in vitro folding stability properties of isolated mutant PAS domain proteins using a thermal unfolding fluorescence assay and a chemical unfolding assay. | pt |
dc.language.iso | eng | pt |
dc.publisher | Public Library of Science | pt |
dc.relation | European Molecular Biology Organization, EMBO (Installation Grant to JHMC) | pt |
dc.relation | SFRH/BD/43896/2008 | pt |
dc.relation | Ciência 2008 | pt |
dc.rights | openAccess | pt |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | pt |
dc.subject.mesh | Circular Dichroism | pt |
dc.subject.mesh | ERG1 Potassium Channel | pt |
dc.subject.mesh | Ether-A-Go-Go Potassium Channels | pt |
dc.subject.mesh | Glycoside Hydrolases | pt |
dc.subject.mesh | HEK293 Cells | pt |
dc.subject.mesh | Humans | pt |
dc.subject.mesh | Long QT Syndrome | pt |
dc.subject.mesh | Phenotype | pt |
dc.subject.mesh | Protein Denaturation | pt |
dc.subject.mesh | Protein Folding | pt |
dc.subject.mesh | Protein Structure, Secondary | pt |
dc.subject.mesh | Protein Structure, Tertiary | pt |
dc.subject.mesh | Protein Transport | pt |
dc.subject.mesh | Temperature | pt |
dc.subject.mesh | Thermodynamics | pt |
dc.subject.mesh | Ultraviolet Rays | pt |
dc.subject.mesh | Mutation | pt |
dc.title | Changes in channel trafficking and protein stability caused by LQT2 mutations in the PAS domain of the HERG channel | pt |
dc.type | article | - |
degois.publication.firstPage | e32654 | pt |
degois.publication.issue | 3 | pt |
degois.publication.title | PLoS ONE | pt |
dc.peerreviewed | yes | pt |
dc.identifier.doi | 10.1371/journal.pone.0032654 | pt |
degois.publication.volume | 7 | pt |
dc.date.embargo | 2012-01-01 | * |
uc.date.periodoEmbargo | 0 | pt |
item.grantfulltext | open | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.openairetype | article | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | Com Texto completo | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.researchunit | CQC - Coimbra Chemistry Centre | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.parentresearchunit | Faculty of Sciences and Technology | - |
crisitem.author.orcid | 0000-0003-1812-1663 | - |
crisitem.author.orcid | 0000-0001-9128-2557 | - |
Appears in Collections: | FCTUC Química - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
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Changes-in-channel-trafficking-and-protein-stability-caused-by-lqt2-mutations-in-the-pas-domain-of-the-herg-channelPLoS-ONE.pdf | 550.21 kB | Adobe PDF | View/Open |
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