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J. Biol. Chem., Vol. 277, Issue 19, 17079-17087, May 10, 2002
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From the Department of Biological Sciences, University of
Pittsburgh, Pittsburgh, Pennsylvania 15260
Conventional kinesin is a highly processive,
plus-end-directed microtubule-based motor that drives membranous
organelles toward the synapse in neurons. Although recent structural,
biochemical, and mechanical measurements are beginning to converge into
a common view of how kinesin converts the energy from ATP turnover into motion, it remains difficult to dissect experimentally the
intermolecular domain cooperativity required for kinesin processivity.
We report here our pre-steady-state kinetic analysis of a kinesin
switch I mutant at Arg210 (NXXSSRSH,
residues 205-212 in Drosophila kinesin). The results show
that the R210A substitution results in a dimeric kinesin that is
defective for ATP hydrolysis and a motor that cannot detach from the
microtubule although ATP binding and microtubule association occur. We
propose a mechanistic model in which ATP binding at head 1 leads to the
plus-end-directed motion of the neck linker to position head 2 forward
at the next microtubule binding site. However, ATP hydrolysis is
required at head 1 to lock head 2 onto the microtubule in a tight
binding state before head 1 dissociation from the microtubule. This
mechanism optimizes forward movement and processivity by ensuring that
one motor domain is tightly bound to the microtubule before the second
can detach.
The Role of ATP Hydrolysis for Kinesin Processivity*
§,¶,
*
This work was supported by National Institutes of Health
Grant GM 54141 (to S. P. G.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
These authors contributed equally to this work.
§
A University of Pittsburgh Honors College Scholar and the recipient
of a Howard Hughes Medical Institute Fellowship, a Barry M. Goldwater Scholarship, and a Norman H. Horowitz Award for
Undergraduate Research.
¶
The recipient of an Andrew Mellon Predoctoral Fellowship.
To whom correspondence should be addressed: Dept. of
Biological Sciences, 518 Langley Hall, University of Pittsburgh,
Pittsburgh, PA 15260. Tel.: 412-624-5842; Fax: 412-624-4759; E-mail:
spg1+@pitt.edu.
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