Title: Molecular modelling insights into DFNA15 mediated enhancement of POU4F3 stability

Authors: Christopher M. Frenz, Philippe P. Lefebvre

Addresses: Department of Otolaryngology, University of Liege, CHU de Liege, 4000 Liege, Belgium. ' Department of Otolaryngology, University of Liege, CHU de Liege, 4000 Liege, Belgium

Abstract: 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 POUHD domain and the POUS domain of the transcription factor.

Keywords: molecular modelling; protein stability; deafness; POU4F3 transcription factor; cochlear hair cells; vestibular hair cells; inner ear; DFNA15 truncation mutation; progressive hearing loss.

DOI: 10.1504/IJCBDD.2008.021429

International Journal of Computational Biology and Drug Design, 2008 Vol.1 No.3, pp.295 - 301

Published online: 26 Nov 2008 *

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