Essential Cell Biology 5th edition

How Proteins Are Controlled
155
Figure 4−49 Changes in conformation can allow a protein to
“walk” along a cytoskeletal filament. This protein cycles between
three different conformations (A, B, and C) as it moves along the
filament. But, without an input of energy to drive its movement in a
single direction, the protein can only wander randomly back and forth,
ultimately getting nowhere.
But how can the changes in shape experienced by proteins be used to
generate such orderly movements? A protein that is required to walk
along a cytoskeletal fiber, for example, can move by undergoing a series
of conformational changes. However, with nothing to drive these changes
in one direction or the other, the shape changes will be reversible and the
protein will wander randomly back and forth (Figure 4−49).
To force the protein to proceed in a single direction, the conformational
changes must be unidirectional. To achieve such directionality, one of the
steps must be made irreversible. For most proteins that are able to move
in a single direction for long distances, this irreversibility is achieved by
coupling one of the conformational changes to the hydrolysis of an ATP
molecule that is tightly bound to the protein—which is why motor proteins
are also ATPases. A great deal of free energy is released when ATP is
hydrolyzed, making it very unlikely that the protein will undergo a reverse
shape change—as required for moving backward. (Such a reversal would
require that the ATP hydrolysis be reversed, by adding a phosphate molecule
to ADP to form ATP.) As a consequence, the protein moves steadily
forward (Figure 4−50).
Many different motor proteins generate directional movement by using
the hydrolysis of a tightly bound ATP molecule to drive an orderly series
of conformational changes. These movements can be rapid: the muscle
motor protein myosin walks along actin filaments at about 6 μm/sec during
muscle contraction (discussed in Chapter 17).
Proteins Often Form Large Complexes That Function as
Machines
As proteins progress from being small, with a single domain, to being
larger with multiple domains, the functions they can perform become
more elaborate. The most complex tasks are carried out by large protein
assemblies formed from many protein molecules. Now that it is possible
to reconstruct biological processes in cell-free systems in a test tube, it
is clear that each central process in a cell—including DNA replication,
gene transcription, protein synthesis, vesicle budding, and transmembrane
signaling—is catalyzed by a highly coordinated, linked set of many
proteins. For most such protein machines, the hydrolysis of bound
nucleoside triphosphates (ATP or GTP) drives an ordered series of conformational
changes in some of the individual protein subunits, enabling
A
B
C
B
C
A
C
B
C
B
A
A
P PP
B
P
A
P P
C
ECB5 04.49
P
A
ATP
BINDING
ATP HYDROLYSIS
CREATES AN
IRREVERSIBLE STEP
A P P
RELEASE OF
ADP AND P i
direction of
movement
Figure 4−50 A schematic model of how a motor protein uses ATP hydrolysis to move in one direction along a cytoskeletal
filament. An orderly transition among three conformations is driven by the hydrolysis of a bound ATP molecule and the release of
the products, ADP and inorganic phosphate (P i ). Because these transitions are coupled to the hydrolysis of ATP, the entire cycle is
essentially irreversible. Through repeated cycles, the protein moves continuously to the right along the filament.