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 POUHD domain and the POUS domain of the transcription factor.