Kinesin's backsteps under mechanical load

Abstract

Kinesins move processively toward the plus end of microtubules by hydrolyzing ATP for each step. From an enzymatic perspective, the mechanism of mechanical motion coupled to the nucleotide chemistry is often well explained using a single-loop cyclic reaction. However, several difficulties arise in interpreting kinesin's backstepping within this framework, especially when external forces oppose the motion of kinesin. We review evidence, such as an ATP-independent stall force and a slower cycle time for backsteps, that has emerged to challenge the idea that kinesin backstepping is due to ATP synthesis, i.e., the reverse cycle of kinesin's forward-stepping chemomechanics. Supplementing the conventional single-loop chemomechanics with routes for ATP-hydrolyzing backward steps and nucleotide-free steps, especially under load, gives a better physical interpretation of the experimental data on backsteps.

5 figures and 2 tables

References in corpus (3)

• Tug-of-war as a cooperative mechanism for bidirectional cargo transport by molecular motors
• Internal strain regulates the nucleotide binding site of the kinesin leading head
• Mechanical control of the directional stepping dynamics of the kinesin motor

Cited by in corpus (14)

• Energetic costs, precision, and efficiency of a biological motor in cargo transport
• Theoretical Perspectives on Biological Machines
• Noise-induced acceleration of single molecule kinesin-1
• A structural perspective on the dynamics of kinesin motors
• Influence of direct motor-motor interaction in models for cargo transport by a single team of motors
• Fluctuating Currents in Stochastic Thermodynamics II. Energy Conversion and Nonequilibrium Response in Kinesin Models
• Discrete step sizes of molecular motors lead to bimodal non-Gaussian velocity distributions under force
• Thermodynamic uncertainty relation to assess biological processes
• Coarse graining of biochemical systems described by discrete stochastic dynamics
• Tug-of-war of molecular motors: the effects of uneven load sharing
• Role of directional fidelity in multiple extreme performance of F1-ATPase motor
• Stochastic thermodynamics and modes of operation of a ribosome: a network theoretic perspective
• Decoding Single Molecule Time Traces with Dynamic Disorder
• How kinesin waits for ATP affects the nucleotide and load dependence of the stepping kinetics