Shaft Function of Kinesin-1's α4 Helix in the Processive Movement.

Abstract

Kinesin-1 motor is a molecular walking machine constructed with amino acids. The understanding of how those structural elements play their mechanical roles is the key to the understanding of kinesin-1 mechanism. Using molecular dynamics simulations, we investigate the role of a helix structure, α4 (also called switch-II helix), of kinesin-1's motor domain in its processive movement along microtubule. Through the analysis of the structure and the interactions between α4 and the surrounding residues in different nucleotide-binding states, we find that, mechanically, this helix functions as a shaft for kinesin-1's motor-domain rotation and, structurally, it is an amphipathic helix ensuring its shaft functioning. The hydrophobic side of α4 consists strictly of hydrophobic residues, making it behave like a lubricated surface in contact with the core β-sheet of kinesin-1's motor domain. The opposite hydrophilic side of α4 leans firmly against microtubule with charged residues locating at both ends to facilitate its positioning onto the intra-tubulin groove. The special structural feature of α4 makes for an effective reduction of the conformational work in kinesin-1's force generation process.