The Electrostatic Mechanism Of Single-Head Molecule Motor KIF1A

Movement is one of the most characteristic feature of life, so we can say"where there's life,there's movement", Most biological movements are accomplished by ingenious protein machines termd molecular motors. All of them have a common feature that they undergo energy-dependent conformational changes that result in unidirectional movements. The energy is from hydrolysising of ATP. These motor take nanometer steps along protein tracks in the cytoplasm and transport a wide variety of cargo, power cell locomotion, drive cell division and, when combined in large ensembles, allow organisms to move. Kinesin is a kind of these motor that walks along microtubule. Although we have known more about the function of kinesin, it is delude that the detail mechanism of how kinesin converts the energy of ATP to mechanical movement and how kinesin achieves periotic steps progressing to the plus end of microtubule.In order to detect the mechanism of kinesin, we take KIF1A as an example which is a kind of single-head kinesin and can takes about 700 steps before detaching from microtubules. As the critical residues of kinesin are primarily positively charged, the electrostatic interaction must plays a main role in interaction with the negatively charged tubulin molecule when kinesin walks on the surface of microtubule. Based on the previous researches and the reported crystal strctures of KIF1A, we utilize the Poisson-Boltzmann equation to study the electrostatic mechanism of KIF1A. By calculating we find: Firstly, the electrostatic energy between KIF1A and microtubule is rigorously periodic, So the electrostatic potential of microtubule likely plays a significant role in ensuring KIF1A progress directionally to the plus end of the microtubule; Secondly, we find there is an actively detaching state when KIF1A completed hydrolysis of ATP, and KIF1A has the lowest electrostatic interaction with microtubule in this state. But the lowest interaction site is not in its binding site at this moment, With the impeling of electrostatic force and strains, KIF1A favorably detaches from the binding site of microtubule; Thirdly, there is a intergrade for KIF1A from weak-binding state to strong-binding state and KIF1A completed find the binding site at the moment. Based on the homology model structure of this state, we find the electrostatic force play a critical role in helping KIF1A correctly recognizing the binding site; At last, we give an integrally electrostatic mechanism of KIF1A. Although these findings are based on a single-head kinesin, it may give a new perspective to study kinesin and the other molecule motors.