Mechanism of the single-headed processivity: Diffusional anchoring betweenthe K-loop of kinesin and the C terminus of tubulin

A motor-domain construct of KIF1A, a single-headed kinesin superfamily prot ein, was demonstrated to take more than 600 steps before detaching from a m icrotubule. However, its molecular mechanism remained unclear. Here we demo nstrate the nucleotide-dependent binding between the lysine-rich, highly po sitively charged loop 12 of the KIF1A motor domain (K-loop) and the glutama te-rich, highly negatively charged C-terminal region of tubulin (E-hook), T his binding did not contribute in the strong binding state but only in the weak binding state. This binding was demonstrated to be essential for the s ingle-headed processivity by functioning as the anchor for the one-dimensio nal simple Brownian movement in the weak binding state. This Brownian movem ent will allow the small KIF1A motor domain to span the distance between th e binding sites on microtubule and also will give the diffusive nature to t he movement of single KIF1A molecules. These observations quantitatively fi tted well to the predictions made from our Brownian motor model on the mech anism of the single-headed processive movement.