What role does dad's basic region play in mdia's auto-inhibition mechanism? A computational study

CHED 892

Susan K. Munster, skmunster@yahoo.com, Chemistry Department, Grand Valley State University, Allendale, MI 49401 and Mary E. Karpen, karpenm@gvsu.edu, Department of Chemistry, Grand Valley State University, 353 Padnos Hall, Allendale, MI 49401.
Mammalian diaphanous-related formins (mDia) activate cytoskeletal actin growth. These essential proteins, which may play a role in cancer, have an auto-inhibition mechanism that is not completely understood. One key participant in mDia's auto-inhibition is a basic tail found in the Diaphanous-autoregulatory Domain (DAD) region of the protein. Using Monte Carlo conformational searching, coupled with energy minimization, possible low energy basic tail conformers were explored to investigate how this tail aids DAD binding. We propose the basic tail acts as a mobile anchor, binding a variety of acidic regions found on the adjacent inhibitory domain of mDia.