Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

162 Chapter 3: Proteins
reversible, and the protein can only wander randomly back and forth along the
thread. We can look at this situation in another way. Since the directional movement
of a protein does work, the laws of thermodynamics (discussed in Chapter 2)
demand that such movement use free energy from some other source (otherwise
the protein could be used to make a perpetual motion machine). Therefore, without
an input of energy, the protein molecule can only wander aimlessly.
How can the cell make such a series of conformational changes unidirectional?
To force the entire cycle to proceed in one direction, it is enough to make any one
of the changes in shape irreversible. Most proteins that are able to walk in one
direction for long distances achieve this motion by coupling one of the conformational
changes to the hydrolysis of an ATP molecule that is tightly bound to the
protein. The mechanism is similar to the one just discussed that drives allosteric
protein shape changes by GTP hydrolysis. Because ATP (or GTP) hydrolysis
releases a great deal of free energy, it is very unlikely that the nucleotide-binding
protein will undergo the reverse shape change needed for moving backward—
since this would require that it also reverse the ATP hydrolysis by adding a phosphate
molecule to ADP to form ATP.
In the model shown in Figure 3–75A, ATP binding shifts a motor protein from
conformation 1 to conformation 2. The bound ATP is then hydrolyzed to produce
ADP and inorganic phosphate (P i ), causing a change from conformation 2 to conformation
3. Finally, the release of the bound ADP and P i drives the protein back
to conformation 1. Because the energy provided by ATP hydrolysis drives the transition
2 → 3, this series of conformational changes is effectively irreversible. Thus,
the entire cycle goes in only one direction, causing the protein molecule to walk
continuously to the right in this example.
Many motor proteins generate directional movement through the use of
a similar unidirectional ratchet, including the muscle motor protein myosin,
Figure 3–74 An allosteric “walking”
protein. Although its three different
conformations allow it to wander randomly
back and forth MBoC6 while m3.76/3.68 bound to a thread or a
filament, the protein cannot move uniformly
in a single direction.
1
2
3
myosin V
actin
1
A
ATP
BINDING
P PP
2
HYDROLYSIS
(A)
P
A
P P
A P P
ADP
RELEASE
P
direction of
movement
3
1
(B)
50 nm
Figure 3–75 How a protein can walk
in one direction. (A) An allosteric
motor protein driven by ATP hydrolysis.
The transition between three different
conformations includes a step driven by
the hydrolysis of a bound ATP molecule,
creating a “unidirectional ratchet” that
makes the entire cycle essentially
irreversible. By repeated cycles, the protein
therefore moves continuously to the right
along the thread. (B) Direct visualization
of a walking myosin motor protein by
high-speed atomic force microscopy; the
elapsed time between steps was less than
0.5 sec (see Movie 16.3). (B, modified from
N. Kodera et al., Nature 468:72–76, 2010.
With permission from Macmillan
Publishers Ltd.)