Interaction Between Motor Domains Can Explain the Complex Dynamics of Heterodimeric Kinesins

TL;DR

This paper presents a stochastic model explaining how interactions between motor domains in heterodimeric kinesins influence their movement, aligning with experimental data and revealing coordinated dynamics.

Contribution

The study introduces a discrete stochastic model that accounts for domain interactions in heterodimeric kinesins, explaining their coordinated motion and differing transition rates.

Findings

Motor domain interactions modify energy landscapes.

Kinesins still move via hand-over-hand mechanism.

Model predictions align with experimental observations.

Abstract

Motor proteins are active enzyme molecules that play a crucial role in many biological processes. They transform the chemical energy into the mechanical work and move unidirectionally along rigid cytoskeleton filaments. Single-molecule experiments suggest that motor proteins, consisting of two motor domains, move in a hand-over-hand mechanism when each subunit changes between trailing and leading positions in alternating steps, and these subunits do not interact with each other. However, recent experiments on heterodimeric kinesins suggest that the motion of motor domains is not independent, but rather strongly coupled and coordinated, although the mechanism of these interactions are not known. We propose a simple discrete stochastic model to describe the dynamics of homodimeric and heterodimeric two-headed motor proteins. It is argued that interactions between motor domains modify free energy landscapes of each motor subunit, and motor proteins still move via the hand-over-hand mechanism but with different transitions rates. Our calculations of biophysical properties agree with experimental observations. Several ways to test the theoretical model are proposed.