Linked Life Data

21752024

Source:http://linkedlifedata.com/resource/pubmed/id/21752024

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-9-2
pubmed:abstractText
Thanatos-associated [THAP] domain-containing apoptosis-associated protein 1 (THAP1) is a DNA-binding protein that has been recently associated with DYT6 dystonia, a hereditary movement disorder involving sustained, involuntary muscle contractions. A large number of dystonia-related mutations have been identified in THAP1 in diverse patient populations worldwide. Previous reports have suggested that THAP1 oligomerizes with itself via a C-terminal coiled-coil domain, raising the possibility that DYT6 mutations in this region might affect this interaction. In this study, we examined the ability of wild-type THAP1 to bind itself and the effects on this interaction of the following disease mutations: C54Y, F81L, ?F132, T142A, I149T, Q154fs180X, and A166T. The results confirmed that wild-type THAP1 associated with itself and most of the DYT6 mutants tested, except for the Q154fs180X variant, which loses most of the coiled-coil domain because of a frameshift at position 154. However, deletion of C-terminal residues after position 166 produced a truncated variant of THAP1 that was able to bind the wild-type protein. The interaction of THAP1 with itself therefore required residues within a 13-amino acid region (aa 154-166) of the coiled-coil domain. Further inspection of this sequence revealed elements highly consistent with previous descriptions of leucine zippers, which serve as dimerization domains in other transcription factor families. Based on this similarity, a structural model was generated to predict how hydrophobic residues in this region may mediate dimerization. These observations offer additional insight into the role of the coiled-coil domain in THAP1, which may facilitate future analyses of DYT6 mutations in this region.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1471-4159
pubmed:author
pubmed:copyrightInfo
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.
pubmed:issnType
Electronic
pubmed:volume
118
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1087-100
pubmed:meshHeading
pubmed-meshheading:21752024-Amino Acid Sequence, pubmed-meshheading:21752024-Apoptosis Regulatory Proteins, pubmed-meshheading:21752024-Cell Fractionation, pubmed-meshheading:21752024-Cell Nucleus, pubmed-meshheading:21752024-Computer Simulation, pubmed-meshheading:21752024-Cytosol, pubmed-meshheading:21752024-DNA, pubmed-meshheading:21752024-DNA-Binding Proteins, pubmed-meshheading:21752024-Dimerization, pubmed-meshheading:21752024-Dystonia Musculorum Deformans, pubmed-meshheading:21752024-Epitopes, pubmed-meshheading:21752024-Fluorescent Antibody Technique, pubmed-meshheading:21752024-Humans, pubmed-meshheading:21752024-Indicators and Reagents, pubmed-meshheading:21752024-Models, Molecular, pubmed-meshheading:21752024-Molecular Sequence Data, pubmed-meshheading:21752024-Mutation, pubmed-meshheading:21752024-Nuclear Localization Signals, pubmed-meshheading:21752024-Nuclear Proteins, pubmed-meshheading:21752024-Plasmids, pubmed-meshheading:21752024-Protein Conformation, pubmed-meshheading:21752024-Transfection, pubmed-meshheading:21752024-Translocation, Genetic
pubmed:year
2011
pubmed:articleTitle
Dimerization of the DYT6 dystonia protein, THAP1, requires residues within the coiled-coil domain.
pubmed:affiliation
Neuroscience Center, Department of Neurology, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural