THE CAVITY IN THE HYDROPHOBIC CORE OF MYB DNA-BINDING DOMAIN IS RESERVED FOR DNA RECOGNITION AND TRANSACTIVATION

The DNA-binding domain of Myb consists of three imperfect repeats, R1, R2 and R3, each containing a helix-turn-helix motif variation. Among these repeats, R2 has distinct characteristics with high thermal insta bility. The NMR structure analysis found a cavity inside the hydrophob ic core of R2 but not in R1 or R3. Here, we show that R2 has slow conf ormational fluctuations, and that a cavity-filling mutation which stab ilizes the R2 structure significantly reduces specific Myb DNA-binding activity and trans-activation. Structural observations of the free an d DNA-complexed states suggest that the implied inherent conformationa l flexibility of R2, associated with the presence of the cavity, could be important for DNA recognition by Myb.