Molecular modelling insights into DFNA15 mediated enhancement of POU4F3 stability.

[en] 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.

Disciplines :

Otolaryngology

Author, co-author :

Frenz, Christopher M

Lefèbvre, Philippe ; Université de Liège - ULiège > Département des sciences cliniques > Oto-rhino-laryngologie et audiophonologie

Language :

English

Title :

Molecular modelling insights into DFNA15 mediated enhancement of POU4F3 stability.

Publication date :

2008

Journal title :

International Journal of Computational Biology and Drug Design

ISSN :

1756-0756

eISSN :

1756-0764

Publisher :

Inderscience Enterprises, United Kingdom

Volume :

Issue :

Pages :

295-301

Peer reviewed :

Peer reviewed

Available on ORBi :

since 30 July 2016

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Bibliography

Baker, N.A., Sept, D., Joseph, S., Holst, M.J. and McCammon, J.A. (2001) ‘Electrostatics of nanosystems: application to microtubules and the ribosome’, PNAS, Vol. 98, pp.10037–10041.
Blom, N., Gammeltoft, S. and Brunak, S. (1999) ‘Sequence and structure based prediction of eukaryotic phosphorylation sites’, Journal of Molecular Biology, Vol. 294, pp.1351–1362.
Comeau, S.R., Gatchell, D.W., Vajda, S. and Camacho, C.J. (2004a) ‘ClusPro: an automated docking and discrimination method for the prediction of protein complexes’, Bio informatics, Vol. 20, pp.45–50.
Comeau, S.R., Gatchell, D.W., Vajda, S. and Camacho, C.J. (2004b) ‘ClusPro: a fully automated algorithm for protein-protein docking’, Nucleic Acids Research, Vol. 32, pp.W96–W99.
Dolinsky, T.J., Nielson, J.E., McCammon, J.A. and Baker, N.A. (2004) ‘PDB2PQR: an automated pipeline for the setup of Poisson-Boltzmann electrostatic calculation’, Nucleic Acids Research, Vol. 32, pp.W665–667.
Erkman, L., McEvilly, R.J., Luo, L., Ryan, A.K., Hooshmand, F., O’Connell, S.M., Keithley, E.M., Rapaport, D.H., Ryan, A.F. and Rosenfeld, M.G. (1996) ‘Role of transcription factors Brn-3.1 and Brn-3.2 in auditory and visual system development’, Nature, Vol. 381, pp.603–606.
Frydman, M., Vreugde, S., Nageris, B.I., Weiss, S., Vahava, O. and Avraham, K.B. (2000) ‘Clinical characterisation of genetic hearing loss caused by a mutation in the POU4F3 transcription factor’, Arch Otolaryngol Head Neck Surg., Vol. 126, pp.633–637.
Lambert, C., Leonard, N., De Bolle, X. and Depiereux, E. (2002) ‘EsyPred3D: prediction of proteins 3D structures’, Bio informatics, Vol. 18, pp.1250–1256.
Letunic, I., Copely, R.R., Schmidt, S., Ciccarelli, F.D., Doerks, T., Schultz, J., Ponting, C.P. and Bork, P. (2004) ‘SMART 4.0: towards genomic data integration’, Nucleic Acids Research. Vol. 32, pp.D142–D144.
Rechsteiner, M. and Rogers, S.W. (1996) ‘PEST sequences and regulation by proteolysis’, TIBS, Vol. 21, pp.267–271.
Rodriguez, R., Chinea, G., Lopez, N., Pons, T. and Vriend, G. (1998) ‘Homology modelling, model and software evaluation: three related resources’, CABIOS, Vol. 14, pp.523–528.
Rogers, S., Wells, R. and Rechsteiner, M. (1986) ‘Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis’, Science, Vol. 234, pp.364–368.
Sali, A., Sanchez, R. and Badretdinov, A. (1997) Modeller: A Program for Protein Structure Modelling Release 4.
Sali, A. and Blundell, T.L. (1993) ‘Comparative protein modelling by satisfaction of spatial restraints’, J. Mol. Biol., Vol. 234, pp.779–815.
Schnell, J.D. and Hicke, L. (2003) ‘Non-traditional functions of ubiquitin and ubiquitin-binding proteins’, J. Biol. Chem., Vol. 278, pp.35857–35860.
Schymkowitz, J., Borg, J., Stricher, F., Nys, R., Rousseau, F. and Serrano, L. (2005) ‘The foldx web server: an online force field’, Nucleic Acids Research, Vol. 33, pp.W382–W388.
Segil, N., Roberts, S.B and Heintz, N. (1991) ‘Mitotic phosphorylation of the 1st October homeodomain and regulation of 1st October DNA binding activity’, Science, Vol. 254, pp.1814–1816.
Sturm, R.A. and Herr, W. (1988) ‘The POU domain is a bipartite DNA-binding structure’, Nature, Vol. 336, pp.601–604.
Ten Eyck, L.F., Mandell, J., Roberts, V.A. and Pique, M.E. (1995) ‘Surveying molecular interactions with DOT’, in Hayes, A. and Simmons, M. (Eds.): Proceeding of the 1995 ACM/IEEE Supercomputing Conference, ACM Press. New York.
Wang, J.M., Cieplak, P. and Kollman, P. (2000) ‘How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules?’, J. Comput. Chem., Vol. 21, pp.1049–1074.
Weiss, S., Gottfreid, I., Mayrose, I., Khare, S.L., Xiang, M., Dawson, S.J. and Avraham, K.B. (2003) ‘The DFNA15 deafness mutation affects POU4F3 protein stability, localisation, and transcriptional activity’, Molecular and Cellular Biology, Vol. 23, pp.7957–7964.
Xiang, M., Gan, L., Li, D., Chen, Z.Y., Zhou, L., O’Malley, B.W., Klein, W. and Nathans, J. (1997) ‘Essential role of POU-domain factor Brn-3c in auditory and vestibular hair cell development’, PNAS, Vol. 94, pp.9445–9450.