Solution Structure of the Lis1/Ndel1 Complex, a regulator of

Cytoplasmic dynein is a microtubule minus-end directed molecular motor. It is involved in key cellular activities including axonal transport, polarized cell division, and anaphase chromosome movement. Lis1 has recently emerged as one of the key regulators of dynein. Lis1 acts on dynein mainly through a complex with its co-regulator Ndel1. The determination of the solution structure of such complex is the subject of the SAXS experiment we report on. We have previously determined the crystal structure of Lis1’s beta propeller containing C-terminal domain [1]. Together with the determination of its N-terminal dimerization domain [2], we now have a complete picture of the molecule. Moreover, we have mapped the Ndel1 binding determinant by site directed mutagenesis of surface residue of Lis1 that are strictly conserved among homologs. Ndel1 is a coiled-coil protein that is able to bind both Lis1 and dynein. We have focused our attention on the Lis1 binding domain by solving the crystal structure of the 190 aa N-terminal coiled coil domain [3]. Moreover we have characterized Ndel1’s Lis1 binding domain by mutagenesis and truncation studies and performed a thorough biochemical and biophysical charactherization of bot