Poster #RP207
Use of docking tools and MD simulations to predict the interaction between the MH2 domain of Smad3 and the PDZ domain of Erbin
Matthieu Chavent*, Claire Nourry**, Nadine Deliot**, Jean Paul Borg**, Bernard Maigret*
*eDAM group - UMR 7565 - H. poincaré University - Nancy 1; **centre de recherche en cancérologie Marseille Inserm Institut Paoli-Calmettes - Université de la méditerranée
Erbin was originally identified as a protein that interacts with the receptor tyrosine kinase ErbB2. This protein contains 16 leucine-rich repeats in its amino terminus and a PDZ domain in its carboxy terminus. Recently, Erbin has been identified as a binding partner for Smad3, a major component of the transforming growth factor-beta signaling pathway. Smad3 has a domain organization consisting in an amino-terminal DNA-binding domain (MH1) and a carboxy-terminal effector domain (MH2).
Experiments demonstrate that the MH2 domain of Smad3 is required for this interaction, and that the carboxyterminal region of Erbin encompassing residues 914 to 1257, plus the PDZ domain are involved.
In this poster, we present how the use of the bioinformatic and molecular modelling tools helped us to conceptualize the association between the Smad3 MH2 and the Erbin PDZ domains. Two models for this association were proposed: one in which the partners were positionned according to the available experimental data and the other using the ClusPro automatic docking web server. 20 ns molecular dynamic simulations were carried out for the two models in order to evaluate their stability. The two models converge to a unique PDZ/MH2 complex in which we defined key residues to be further mutated.