Kinesin processivity is gated by phosphate release

Bojan Milic, Johan O.L. Andreasson, William O. Hancock, Steven M. Block

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Kinesin-1 is a dimeric motor protein, central to intracellular transport, that steps hand-over-hand toward the microtubule (MT) plus-end, hydrolyzing one ATP molecule per step. Its remarkable processivity is critical for ferrying cargo within the cell: over 100 successive steps are taken, on average, before dissociation from the MT. Despite considerable work, it is not understood which features coordinate, or "gate," the mechanochemical cycles of the two motor heads. Here, we show that kinesin dissociation occurs subsequent to, or concomitant with, phosphate (Pi) release following ATP hydrolysis. In optical trapping experiments, we found that increasing the steady-state population of the posthydrolysis ADPPistate (by adding free Pi) nearly doubled the kinesin run length, whereas reducing either the ATP binding rate or hydrolysis rate had no effect. The data suggest that, during processive movement, tethered-head binding occurs subsequent to hydrolysis, rather than immediately after ATP binding, as commonly suggested. The structural change driving motility, thought to be neck linker docking, is therefore completed only upon hydrolysis, and not ATP binding. Our results offer additional insights into gating mechanisms and suggest revisions to prevailing models of the kinesin reaction cycle.

Original languageEnglish (US)
Pages (from-to)14136-14140
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number39
DOIs
StatePublished - Sep 30 2014

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Kinesin
Adenosine Triphosphate
Phosphates
Hydrolysis
Microtubules
Hand
Optical Tweezers
Head Movements
Neck
Head
Population
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Milic, Bojan ; Andreasson, Johan O.L. ; Hancock, William O. ; Block, Steven M. / Kinesin processivity is gated by phosphate release. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 39. pp. 14136-14140.
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Kinesin processivity is gated by phosphate release. / Milic, Bojan; Andreasson, Johan O.L.; Hancock, William O.; Block, Steven M.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 39, 30.09.2014, p. 14136-14140.

Research output: Contribution to journalArticle

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