The mechanochemical cycle of mammalian kinesin-2 KIF3A/B under load

Johan O.L. Andreasson, Shankar Shastry, William O. Hancock, Steven M. Block

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

The response of motor proteins to external loads underlies their ability to work in teams and determines the net speed and directionality of cargo transport. The mammalian kinesin-2, KIF3A/B, is a heterotrimeric motor involved in intraflagellar transport and vesicle motility in neurons. Bidirectional cargo transport is known to result from the opposing activities of KIF3A/B and dynein bound to the same cargo, but the load-dependent properties of kinesin-2 are poorly understood. We used a feedback-controlled optical trap to probe the velocity, run length, and unbinding kinetics of mouse KIF3A/B under various loads and nucleotide conditions. The kinesin-2 motor velocity is less sensitive than kinesin-1 to external forces, but its processivity diminishes steeply with load, and the motor was observed occasionally to slip and reattach. Each motor domain was characterized by studying homodimeric constructs, and a global fit to the data resulted in a comprehensive pathway that quantifies the principal force-dependent kinetic transitions. The properties of the KIF3A/B heterodimer are intermediate between the two homodimers, and the distinct load-dependent behavior is attributable to the properties of the motor domains and not to the neck linkers or the coiled-coil stalk. We conclude that the force-dependent movement of KIF3A/B differs significantly from conventional kinesin-1. Against opposing dynein forces, KIF3A/B motors are predicted to rapidly unbind and rebind, resulting in qualitatively different transport behavior from kinesin-1.

Original languageEnglish (US)
Pages (from-to)1166-1175
Number of pages10
JournalCurrent Biology
Volume25
Issue number9
DOIs
StatePublished - May 4 2015

Fingerprint

Kinesin
kinesin
Dyneins
Optical Tweezers
Transport Vesicles
Aptitude
kinetics
Kinetics
Neck
probes (equipment)
neck
Nucleotides
Neurons
neurons
nucleotides
Feedback
mice
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Andreasson, Johan O.L. ; Shastry, Shankar ; Hancock, William O. ; Block, Steven M. / The mechanochemical cycle of mammalian kinesin-2 KIF3A/B under load. In: Current Biology. 2015 ; Vol. 25, No. 9. pp. 1166-1175.
@article{b8c4f04cc1b343d2a3ee533e753a768d,
title = "The mechanochemical cycle of mammalian kinesin-2 KIF3A/B under load",
abstract = "The response of motor proteins to external loads underlies their ability to work in teams and determines the net speed and directionality of cargo transport. The mammalian kinesin-2, KIF3A/B, is a heterotrimeric motor involved in intraflagellar transport and vesicle motility in neurons. Bidirectional cargo transport is known to result from the opposing activities of KIF3A/B and dynein bound to the same cargo, but the load-dependent properties of kinesin-2 are poorly understood. We used a feedback-controlled optical trap to probe the velocity, run length, and unbinding kinetics of mouse KIF3A/B under various loads and nucleotide conditions. The kinesin-2 motor velocity is less sensitive than kinesin-1 to external forces, but its processivity diminishes steeply with load, and the motor was observed occasionally to slip and reattach. Each motor domain was characterized by studying homodimeric constructs, and a global fit to the data resulted in a comprehensive pathway that quantifies the principal force-dependent kinetic transitions. The properties of the KIF3A/B heterodimer are intermediate between the two homodimers, and the distinct load-dependent behavior is attributable to the properties of the motor domains and not to the neck linkers or the coiled-coil stalk. We conclude that the force-dependent movement of KIF3A/B differs significantly from conventional kinesin-1. Against opposing dynein forces, KIF3A/B motors are predicted to rapidly unbind and rebind, resulting in qualitatively different transport behavior from kinesin-1.",
author = "Andreasson, {Johan O.L.} and Shankar Shastry and Hancock, {William O.} and Block, {Steven M.}",
year = "2015",
month = "5",
day = "4",
doi = "10.1016/j.cub.2015.03.013",
language = "English (US)",
volume = "25",
pages = "1166--1175",
journal = "Current Biology",
issn = "0960-9822",
publisher = "Cell Press",
number = "9",

}

The mechanochemical cycle of mammalian kinesin-2 KIF3A/B under load. / Andreasson, Johan O.L.; Shastry, Shankar; Hancock, William O.; Block, Steven M.

In: Current Biology, Vol. 25, No. 9, 04.05.2015, p. 1166-1175.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The mechanochemical cycle of mammalian kinesin-2 KIF3A/B under load

AU - Andreasson, Johan O.L.

AU - Shastry, Shankar

AU - Hancock, William O.

AU - Block, Steven M.

PY - 2015/5/4

Y1 - 2015/5/4

N2 - The response of motor proteins to external loads underlies their ability to work in teams and determines the net speed and directionality of cargo transport. The mammalian kinesin-2, KIF3A/B, is a heterotrimeric motor involved in intraflagellar transport and vesicle motility in neurons. Bidirectional cargo transport is known to result from the opposing activities of KIF3A/B and dynein bound to the same cargo, but the load-dependent properties of kinesin-2 are poorly understood. We used a feedback-controlled optical trap to probe the velocity, run length, and unbinding kinetics of mouse KIF3A/B under various loads and nucleotide conditions. The kinesin-2 motor velocity is less sensitive than kinesin-1 to external forces, but its processivity diminishes steeply with load, and the motor was observed occasionally to slip and reattach. Each motor domain was characterized by studying homodimeric constructs, and a global fit to the data resulted in a comprehensive pathway that quantifies the principal force-dependent kinetic transitions. The properties of the KIF3A/B heterodimer are intermediate between the two homodimers, and the distinct load-dependent behavior is attributable to the properties of the motor domains and not to the neck linkers or the coiled-coil stalk. We conclude that the force-dependent movement of KIF3A/B differs significantly from conventional kinesin-1. Against opposing dynein forces, KIF3A/B motors are predicted to rapidly unbind and rebind, resulting in qualitatively different transport behavior from kinesin-1.

AB - The response of motor proteins to external loads underlies their ability to work in teams and determines the net speed and directionality of cargo transport. The mammalian kinesin-2, KIF3A/B, is a heterotrimeric motor involved in intraflagellar transport and vesicle motility in neurons. Bidirectional cargo transport is known to result from the opposing activities of KIF3A/B and dynein bound to the same cargo, but the load-dependent properties of kinesin-2 are poorly understood. We used a feedback-controlled optical trap to probe the velocity, run length, and unbinding kinetics of mouse KIF3A/B under various loads and nucleotide conditions. The kinesin-2 motor velocity is less sensitive than kinesin-1 to external forces, but its processivity diminishes steeply with load, and the motor was observed occasionally to slip and reattach. Each motor domain was characterized by studying homodimeric constructs, and a global fit to the data resulted in a comprehensive pathway that quantifies the principal force-dependent kinetic transitions. The properties of the KIF3A/B heterodimer are intermediate between the two homodimers, and the distinct load-dependent behavior is attributable to the properties of the motor domains and not to the neck linkers or the coiled-coil stalk. We conclude that the force-dependent movement of KIF3A/B differs significantly from conventional kinesin-1. Against opposing dynein forces, KIF3A/B motors are predicted to rapidly unbind and rebind, resulting in qualitatively different transport behavior from kinesin-1.

UR - http://www.scopus.com/inward/record.url?scp=84927741846&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84927741846&partnerID=8YFLogxK

U2 - 10.1016/j.cub.2015.03.013

DO - 10.1016/j.cub.2015.03.013

M3 - Article

C2 - 25866395

AN - SCOPUS:84927741846

VL - 25

SP - 1166

EP - 1175

JO - Current Biology

JF - Current Biology

SN - 0960-9822

IS - 9

ER -