Molecular modelling insights into DFNA15 mediated enhancement of POU4F3 stability.
The POU4F3 transcription factor is expressed in the cochlear and vestibular hair cells of the inner ear and its targeted deletion results in a loss of inner ear hair cells. The DFNA15 truncation mutation has been demonstrated to result in a loss of transcriptional activity, but an increase in the stability of the protein. Molecular modelling is utilised to propose a mechanism of stability enhancement, via an interaction between the truncated POU(HD) domain and the POU(S) domain of the transcription factor.
Frenz
Christopher M
CM
Department of Otolaryngology, University of Liege, CHU de Liege, 4000 Liege, Belgium. cfrenz@gmail.com
Lefebvre
Philippe P
PP
D019295:Computational Biology; D003198:Computer Simulation; D030562:Databases, Protein; D006207:Half-Life; D018398:Homeodomain Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008958:Models, Molecular; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D017384:Sequence Deletion; D055672:Static Electricity; D040681:Structural Homology, Protein; D013816:Thermodynamics; D050821:Transcription Factor Brn-3C / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
D018398:Homeodomain Proteins; C111223:POU4F3 protein, human; D050821:Transcription Factor Brn-3C