Electrostatic interactions between the microtubule body and motor proteins: from the initial capture, navigation to the binding site to final release

Abstract

Cells have a transport system that consists of microtubules (MTs) and the associated motor proteins: dynein and kinesin. MTs and motors work together to power many processes essential to eukaryotic life, such as cell migration and division. One remarkable yet relatively overlooked property of MTs is their electrostatics, primarily dominated by the high density of negatively charged amino acids on their surface]. Here we review how the electrostatic field around the MT influences the interactions with motor proteins: from the initial capture, the navigation toward the binding site, to the final release. We compare how kinesin family members interact with the MT and relate that to the difference in charged residues carried by the motors. The picture that emerges: a motor protein approaching the MT from a distance is captured more often by the electronegative field when it has a higher net charge. The magnitude of this effect depends heavily on the extent of screening of protein charges by ions in the surroundings. Of special interest are the highly dynamic and negatively charged C-terminal tails (CTTs) of tubulin that protrude from the MT surface. These tails generate an intermediate state where the motor is weakly attached but kept close to the MT. On the MT surface, the electrostatic field resembles a hilly landscape; the motor is steered to its binding site by an interplay between that field and the charged residues on the motor itself. This guidance can speed up the binding of a motor domain, enhancing the number of steps a motor takes and thereby its run length. The latter is also increased via units of positively charged residues that can electrostatically tether the motor to the MT. This stabilises a weak state, allowing for reattachment and preventing release. When force is applied, a high affinity for this weak interaction state, mediated by non-specific charge interactions, gives motors lower processivity and makes them slip back. Electrostatics direct the dynamic properties of MT-binding proteins in a myriad of ways, an aspect that has frequently been overlooked in cell biology and in vitro studies. Charges warrant the focus of those who want to fully comprehend the MTs and their motors