Biomedical Engineering Reference
In-Depth Information
tramolecular strain of the two heads of a myosin V dimer by subjecting single
myosin V heads to either forward or backward loads of 2 pN. The backward
load causes myosin V heads to detach more slowly from the actin filament
independent of ATP concentration, while forward loads result in detachment
rates that are consistent with unloaded ATPase assays. These results are con-
sistent with backward loads slowing the weak-to-strong transition of myosin
V
ADP [64]. Thus, the leading head of myosin V may be gated by internal
strain in the molecule.
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5.4.3 Gating and Step Size
Gating would explain one other seemingly perplexing property of kinesin,
myosin V, and myosin VI. All of these motors seem structurally capable of
taking many different-sized steps on their partner filaments, based on a simple
comparison of motor geometries to filament geometries. Despite this, kinesin
and myosin V both have fairly tightly distributed, load-independent step sizes
[48, 49, 70, 71]. The step sizes of myosin VI and dynein are more variable than
those of kinesin and myosin V, but it appears structurally possible that these
motors could have far more variability in their step size than is measured
[50, 51]. The gating mechanisms of these motors may result in internal strain
strictly limiting the number of enzymatically active positions of motor heads
on their partner filaments and thus limiting the sizes of steps these motors
take. While this is an attractive idea, it is dicult to measure internal strain
in molecular motors.
5.4.4 Gating in Nonprocessive Motors?
Gating mechanisms can make motors nonprocessive as well as processive. Sin-
gle molecules of the kinesin family member, ncd cannot take multiple mechan-
ical steps on the microtubule before dissociating [62]. Structural and mecha-
nistic studies on ncd revealed that the unbound head of ncd is never positioned
such that it can bind to microtubules at the same time as the bound head,
and the velocity and ATPase activity of a single-headed ncd heterodimer is
the same as wild-type ncd [72]. Thus, the unbound head cannot bind the
microtubule until the bound head has let go. It is unknown what biological
function is served by this conformationally gated non-processivity of ncd, or
the gating mechanisms of the processive motors either, for that matter. It
is interesting to speculate, however, that because enzymatic mechanisms of
motors are exquisitely sensitive to their conformation, they may be controlled
or regulated very effectively in subtle ways.
5.5 Mechanisms of Motor “Inaction”
Similarities between the mechanical mechanisms of kinesin and myosin were
not apparent at first, but when researchers became aware of them, both motor
