Shaft Function of Kinesin-1's ?4 Helix in the Processive Movement.

ABSTRACT: Introduction: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. Methods:Using molecular dynamics simulations, we investigate the role of a helix structure, ?4 (also called switch-II helix), of kinesin-1's motor domain in its processive movement along microtubule. Results:Through the analysis of the structure and the interactions between ?4 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 ?4 consists strictly of hydrophobic residues, making it behave like a lubricated surface in contact with the core ?-sheet of kinesin-1's motor domain. The opposite hydrophilic side of ?4 leans firmly against microtubule with charged residues locating at both ends to facilitate its positioning onto the intra-tubulin groove. Conclusions:The special structural feature of ?4 makes for an effective reduction of the conformational work in kinesin-1's force generation process.

SUBMITTER: Ma YL 

PROVIDER: S-EPMC6816713 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature