Kinesin Processivity Is Determined by a Kinetic Race from a Vulnerable One-Head-Bound State

Keith J. Mickolajczyk, William O. Hancock

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Kinesin processivity, defined as the average number of steps that occur per interaction with a microtubule, is an important biophysical determinant of the motor's intracellular capabilities. Despite its fundamental importance to the diversity of tasks that kinesins carry out in cells, no existing quantitative model fully explains how structural differences between kinesins alter kinetic rates in the ATPase cycle to produce functional changes in processivity. Here we use high-resolution single-molecule microscopy to directly observe the stepping behavior of kinesin-1 and -2 family motors with different length neck-linker domains. We characterize a one-head-bound posthydrolysis vulnerable state where a kinetic race occurs between attachment of the tethered head to its next binding site and detachment of the bound head from the microtubule. We find that greater processivity is correlated with faster attachment of the tethered head from this vulnerable state. In compliment, we show that slowing detachment from this vulnerable state by strengthening motor-microtubule electrostatic interactions also increases processivity. Furthermore, we provide evidence that attachment of the tethered head is irreversible, suggesting a first passage model for exit from the vulnerable state. Overall, our results provide a kinetic framework for explaining kinesin processivity and for mapping structural differences to functional differences in diverse kinesin isoforms.

Original languageEnglish (US)
Pages (from-to)2615-2623
Number of pages9
JournalBiophysical journal
Volume112
Issue number12
DOIs
StatePublished - Jun 20 2017

All Science Journal Classification (ASJC) codes

  • Biophysics

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