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

152 Chapter 3: Proteins
molecule
X
INACTIVE
glucose
molecule
X
positive
regulation
Figure 3–57 Positive regulation caused
by conformational coupling between
two separate binding sites. In this
example, both glucose and molecule X
bind best to the closed conformation of a
protein with two domains. Because both
glucose and molecule X drive the protein
toward its closed conformation, each
ligand helps the other to bind. Glucose
and molecule X are therefore said to bind
cooperatively to the protein.
ACTIVE
10% active 100% active
The relationships shown in Figures 3–57 and 3–58 apply to all proteins, and
they underlie all of cell biology. The principle seems so obvious in retrospect
that we now take it for granted. But the discovery of linkage in studies of a few
MBoC6 m3.58/3.53
enzymes in the 1950s, followed by an extensive analysis of allosteric mechanisms
in proteins in the early 1960s, had a revolutionary effect on our understanding of
biology. Since molecule X in these examples binds at a site on the enzyme that
is distinct from the site where catalysis occurs, it need not have any chemical
relationship to the substrate that binds at the active site. Moreover, as we have
just seen, for enzymes that are regulated in this way, molecule X can either turn
the enzyme on (positive regulation) or turn it off (negative regulation). By such a
mechanism, allosteric proteins serve as general switches that, in principle, can
allow one molecule in a cell to affect the fate of any other.
Symmetric Protein Assemblies Produce Cooperative Allosteric
Transitions
A single-subunit enzyme that is regulated by negative feedback can at most
decrease from 90% to about 10% activity in response to a 100-fold increase in
the concentration of an inhibitory ligand that it binds (Figure 3–59, red line).
Responses of this type are apparently not sharp enough for optimal cell regulation,
and most enzymes that are turned on or off by ligand binding consist of symmetric
assemblies of identical subunits. With this arrangement, the binding of a molecule
of ligand to a single site on one subunit can promote an allosteric change in
the entire assembly that helps the neighboring subunits bind the same ligand. As
a result, a cooperative allosteric transition occurs (Figure 3–59, blue line), allowing
ACTIVE
molecule
X
molecule
X
INACTIVE
glucose
negative
regulation
100% active 10% active
Figure 3–58 Negative regulation caused
by conformational coupling between
two separate binding sites. The scheme
here resembles that in the previous figure,
but here molecule X prefers the open
conformation, while glucose prefers the
closed conformation. Because glucose
and molecule X drive the protein toward
opposite conformations (closed and open,
respectively), the presence of either ligand
interferes with the binding of the other.