The origin of minus-end directionality and mechanochemistry of Ncd motors.

摘要: Adaptation of molecular structure to the ligand chemistry and interaction with cytoskeletal filament are key understanding mechanochemistry motors. Despite striking structural similarity kinesin-1, which moves towards plus-end, Ncd motors exhibit minus-end directionality on microtubules (MTs). Here, by employing a structure-based model protein folding, we show that simple repositioning neck-helix makes dynamics non-processive directed as opposed kinesin-1. Our computational shows in solution can have both symmetric asymmetric conformations disparate ADP binding affinity, also revealing there is strong correlation between distortion motor head decrease affinity state. The nucleotide (NT) free-ADP (φ-ADP) state bound MTs favors conformation whose coiled-coil stalk points plus-end. Upon ATP binding, an enhanced flexibility near head-neck junction region, identified important element for directional motility, leads reorienting stabilizing conformation. remarkable example demonstrates how proteins kinesin superfamily diversify their functions simply rearranging elements peripheral catalytic domain.