Biology Reference
In-Depth Information
any dielectric object feels a force proportional to the magnitude of the gradient that
pulls the object into the region of maximum field strength. The laser beam therefore
can be used to apply a force to any dielectric particle to manipulate its position
(Ishii and Yanagida 2007). Employing optical tweezers, biophysicists during the
past decade were able to measure simultaneously both the translational motion of
the myosin head (which has the ATPase activity) along actin filament and the
hydrolysis of ATP that powers the myosin movement (Ishijima et al 1998; Ishii and
Yanagida 2007). A typical example of such experiments is shown in Fig.
11.33
.
The single-molecule measurements revealed three distinct states for the ATP-
actomyosin system as schematized in Fig.
11.33d
. In State (1), actin is displaced
from its equilibrium position as indicated by the upper trace in Fig.
11.33d
due to
myosin, free of ATP (as indicated by the low fluorescence level in the lower panel of
Fig.
11.33d
), exerting a force on it. In State (2), myosin rapidly dissociates from actin
which causes a rapid return of actin to its equilibrium position and ATP begins to
bind slowly to the dissociated myosin (which is not too far away from actin) causing
an increase in fluorescence level. In the transient State (3), ATP is rapidly
hydrolyzed by myosin and ADP leaves (as indicated by the precipitous drop in
ATP fluorescence intensity), making the ATP-free myosin exert force on actin.
In State (4), ATP-free myosin keeps actin displaced from its equilibrium position
as in State (1).
In the lower portion of Fig.
11.33d
, Ishii and Yanagida (2007) propose a four-
state (labeled 1-4) mechanism of the myosin movement along the actin filament
driven by ATP hydrolysis. In contrast, the
conformon-based mechanism
of muscle
contraction shown in Fig.
11.31
contains eight steps (labeled
a
-
h
), some of which
correspond to the four states invoked by Ishii and Yanagida (see the numbers in
parentheses in Fig.
11.31
). The Ishii-Yanagida and conformon mechanisms are
compared in Table
11.14
.
As evident in Table
11.14
, the conformon-based mechanism of myosin-actin
interactions can explain every observation accounted for by the mechanism pro-
posed by Ishii and Yanagida (2000, 2007) and, in addition, provides reasonable
explanations (i.e., two conformons generated per ATP hydrolysis event) as to why
there are two 5.5-nm steps per turnover of the actomyosin system. The single-
molecule mechanical measurements of the actomyosin system presented in
Fig.
11.33
seem to support the conformon model of muscle contraction proposed
in Ji (1974b). To evaluate the validity of this conclusion, the pictorial version of the
conformon-based model of muscle contraction is reproduced in Fig.
11.34
.
According to the conformon model, two processes are crucial in muscle con-
traction: (a) the transduction of the chemical free energy of ATP to conformons
stored in myosin. In State a, one molecule of ATP is bound to S-1 and myosin is in
its ground state (as symbolized by a relaxed spring). Brownian motions (also called
thermal fluctuations) bring S-1 close to the myosin-binding site on the thin filament
(see the upper bar with two indentations) that is located on the Z-line side of myosin
(see a
b). Upon binding actin, myosin catalyzes the phosphoryl group transfer
from the bound ATP to a hypothetical phosphoryl group acceptor X located in S-1
(see b). The exergonic nature of this reaction enables the following two events
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