Structural Fluctuations of Microtubule Binding Site of KIF1A in Different Nucleotide States

TL;DR

This study uses molecular dynamics simulations to reveal how the flexibility of a specific helix in KIF1A varies with nucleotide states, affecting its microtubule binding affinity.

Contribution

It uncovers the structural fluctuation patterns of the alpha4 helix in KIF1A across different nucleotide states, linking flexibility to binding affinity regulation.

Findings

Alpha4 helix fluctuation correlates with nucleotide state.

Large fluctuation frequency relates to microtubule affinity.

Thermal fluctuation strength influences binding site dynamics.

Abstract

How molecular motors like Kinesin regulates the affinity to the rail protein in the process of ATP hydrolysis remains to be uncovered. To understand the regulation mechanism, we investigate the structural fluctuation of KIF1A in different nucleotide states that are realized in the ATP hydrolysis process by molecular dynamics simulations of Go-like model. We found that "alpha4 helix", which is a part of the microtubule (MT) binding site, changes its fluctuation systematically according to the nucleotide states. In particular, the frequency of large fluctuations of alpha4 strongly correlates with the affinity of KIF1A for microtubule. We also show how the strength of the thermal fluctuation and the interaction with the nucleotide affect the dynamics of microtubule binding site. These results suggest that KIF1A regulates the affinity to MT by changing the flexibility of alpha4 helix according to the nucleotide states.