Paper Citing NAMD - Abstract
Bouard, Charlotte; Terreux, Raphael; Hope, Jennifer; Chemelle, Julie Anne; Puisieux, Alain; Ansieau, Stephane; Payen, Lea
Interhelical loops within the bHLH domain are determinant in maintaining TWIST1-DNA complexes
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS, 32:226-241, FEB 1 2014
The basic helix-loop-helix (bHLH) transcription factor TWIST1 is essential to embryonic development, and hijacking of its function contributes to the development of numerous cancer types. It forms either a homodimer or a heterodimeric complex with an E2A or HAND partner. These functionally distinct complexes display sometimes antagonistic functions during development, so that alterations in the balance between them lead to pronounced morphological alterations, as observed in mice and in Saethre-Chotzen syndrome patients. We, here, describe the structures of TWIST1 bHLH-DNA complexes produced in silico through molecular dynamics simulations. We highlight the determinant role of the interhelical loops in maintaining the TWIST1-DNA complex structures and provide a structural explanation for the loss of function associated with several TWIST1 mutations/ insertions observed in Saethre-Chotzen syndrome patients.
