Biomedical Engineering Reference
In-Depth Information
RT
ln
forward steps
back steps
ΔG
Bias
=
−
(5.2)
Eciency =
ΔG
Work
(forward steps
−
back steps)
.
(5.3)
5.4 The Processive Motors: The Importance of Gating
A striking behavior of several kinesin, myosin, and dynein family members
that was not predicted by the swinging crossbridge hypothesis is processivity,
which is the ability of a single motor molecule to take several ATP-coupled
steps on its partner filament before dissociating. A critical property of highly
processive motors is gating. When gating occurs in a molecular motor dimer,
the gated head is enzymatically trapped at specific points in the chemome-
chanical cycle of coupled ATPase activity and conformational changes. The
trapped head cannot advance a step in its chemomechanical cycle until the
other head has done so. Gating of the two motor heads has been shown to
be the major determinant of processivity for kinesin, and gating mechanisms
have been observed for several other motor types as well.
5.4.1 Are Processive Motors Always Gated?
It is possible for molecular motors to be processive simply because the two
tethered motor heads in a dimer both spend the majority of their ATPase
cycles tightly bound to their partner filament [59]. However, the duty cycle
(relative amount of time in the ATPase cycle that is spent tightly bound to the
partner filament) of single motor heads correlates poorly with motor proces-
sivity in general. Kinesin takes hundreds of steps without falling off of the mi-
crotubule [60], but its processivity would be extremely low if it were not gated.
ADP-kinesin is not tightly bound to microtubules [31] and ADP release is the
rate-limiting step in kinesin's enzymatic cycle [32]. The kinesin family mem-
ber ncd, meanwhile, spends the majority of its ATPase cycle tightly bound to
microtubules [61], but ncd is categorically nonprocessive: it never steps twice
on the microtubule without falling off [62]. The processive myosins V and VI
both spend the majority of their ATPase cycles bound to actin. Therefore,
they are predicted to be processive without gating mechanisms [59], but data
on both of these motors has shown that they, too, are gated [59, 63, 64]. Data
from several different techniques is used to demonstrate the gating mecha-
nisms of molecular motors. The data for kinesin, myosin V, myosin VI, and
ncd are discussed in Section 5.4.2.
5.4.2 Gating Mechanisms
Kinesin
The first clear demonstration of gating for a molecular motor was made
by David Hackney in 1994, performing ADP release experiments on kinesin
