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6128685 
Journal Article 
In-depth Characterization of the Homodimerization Domain of the Transcription Factor THAP1 and Dystonia-Causing Mutations Therein 
Richter, A; Hollstein, R; Hebert, E; Vulinovic, F; Eckhold, J; Osmanovic, A; Depping, R; Kaiser, FJ; Lohmann, K 
2017 
Yes 
Journal of Molecular Neuroscience
ISSN: 0895-8696
EISSN: 1559-1166 
62 
1 
11-16 
English 
28299530 
WOS:000401519700002 
Mutations in the THAP1 gene encoding the transcription factor THAP1 have been shown to cause DYT6 dystonia. THAP1 contains a highly conserved THAP zinc finger at its N-terminal region which allows specific binding to its target sequences as well as a coiled-coil domain (amino acids 139-190) towards its C-terminus postulated as a protein-protein-binding motif. While several DYT6-causing mutations within the THAP domain were shown to decrease THAP1 activity in transcriptional regulation and DNA-binding, the role of mutations within the coiled-coil domain is rather unknown. Therefore, assigning a function to this domain may enable functional testing of mutations in this region. Notably, THAP1 and other THAP proteins form homodimers; however, the responsible domain has not been elucidated in detail. We show that the region of amino acids 139-185 is involved in formation of THAP1 homodimers by using yeast-two-hybrid, GST pull-down, and cross-linking assays. Surprisingly, all nine reported DYT6-causing missense mutations within this region had no effect on dimerization of THAP1 in GST pull-down and formaldehyde cross-linking assays. In conclusion, we demonstrated that a region of 47 amino acids is involved in THAP1 homodimerization but mutations in this region seem not to impair this mechanism.