Interactions Between Kinesin And Microtubule In Different Nucleotide Binding State

Microtubule not only provides the walking track for kinesin motor but also modulates kinesin's mechanochemical cycle.It is proved that kinesin binding to microtubule greatly increases the rate of ATP hydrolysis and the rate of ADP release.All these complicated functions of microtubule are accomplished through the interactions between kinesin and microtubule.The interaction between kinesin and microtubule is one of the key points to understand the mechanism of kinesin movement.Based on the newly obtained crystal structures of APO-and ATP-state kinesin-microtubule complexes,we investigate the interactions between kinesin and microtubule,and the interactions between kinesin's nucleotide-binding pocket(NBP)and microtubule using molecular dynamics(MD)simulation and analyze the effects on kinesin-microtubule interactions due to the sequence difference between -and-tubulin.Statistical analysis shows that the interaction strength between kinesin and microtubule is strongest in kinesin's nucleotide-free state and weakest in ADP state.The structural differences between -and -tubulin make kinesin binding to -tubulin much more favorable than to -tubulin.In addition,we investigate the interactions between kinesin's NBP and microtubule using MD simulations.We find that,in addition to the early found indirect interactions between E236 and microtubule via N255,the N-3 motif of NBP has direct interactions with microtubule.