Cellular Structure, Proteins, and Metabolism
69
to the same binding site affects the percentage of binding sites
occupied by any one ligand. If two competing ligands, A and
B, are present, increasing the concentration of A will increase
the amount of A that is bound, thereby decreasing the number
of sites available to B and decreasing the amount of B that is
bound.
As a result of competition, the biological effects of one
ligand may be diminished by the presence of another. For
example, many drugs produce their effects by competing with
the body’s natural ligands for binding sites. By occupying the
binding sites, the drug decreases the amount of natural ligand
that can be bound.
Regulation of Binding Site
Characteristics
Because proteins are associated with practically everything
that occurs in a cell, the mechanisms for controlling these
functions center on the control of protein activity. There are
two ways of controlling protein activity: (1) changing protein
shape, which alters the binding of ligands, and (2) as described
earlier in this chapter, regulating protein synthesis and degra-
dation, which determines the types and amounts of proteins
in a cell.
As described in Chapter 2, a protein’s shape depends on
electrical attractions between charged or polarized groups
in various regions of the protein. Therefore, a change in the
charge distribution along a protein or in the polarity of the
molecules immediately surrounding it will alter its shape. The
two mechanisms used by cells to selectively alter protein shape
are known as allosteric modulation and covalent modulation.
Before we describe these mechanisms, however, it should be
emphasized that only certain key proteins are regulated by
modulation. Most proteins are not subject to either of these
types of modulation.
Allosteric Modulation
Whenever a ligand binds to a protein, the attracting forces
between the ligand and the protein alter the protein’s shape. For
example, as a ligand approaches a binding site, these attracting
forces can cause the surface of the binding site to bend into a
shape that more closely approximates the shape of the ligand’s
surface.
Moreover, as the shape of a binding site changes, it pro-
duces changes in the shape of
other
regions of the protein, just
as pulling on one end of a rope (the polypeptide chain) causes
the other end of the rope to move. Therefore, when a pro-
tein contains
two
binding sites, the noncovalent binding of a
ligand to one site can alter the shape of the second binding site
and, therefore, the binding characteristics of that site. This is
termed
allosteric
(other shape)
modulation
(
Figure 3–32a
),
and such proteins are known as
allosteric proteins.
One binding site on an allosteric protein, known as the
functional
(or active)
site,
carries out the protein’s physi-
ological function. The other binding site is the
regulatory
site.
The ligand that binds to the regulatory site is known as a
modulator molecule,
because its binding allosterically mod-
ulates the shape, and thus the activity, of the functional site.
The regulatory site to which modulator molecules bind
is the equivalent of a molecular switch that controls the func-
tional site. In some allosteric proteins, the binding of the mod-
ulator molecule to the regulatory site turns on the functional
site by changing its shape so that it can bind the functional
ligand. In other cases, the binding of a modulator molecule
turns off the functional site by preventing the functional site
from binding its ligand. In still other cases, binding of the
modulator molecule may decrease or increase the affi nity of the
functional site. For example, if the functional site is 50 percent
saturated at a particular ligand concentration, the binding of a
modulator molecule that increases the affi nity of the functional
site may increase its saturation to 75 percent. This concept will
be especially important when we consider how gases are bound
to a transport protein in the blood (Chapter 13).
To summarize, the activity of a protein can be increased
without changing the concentration of either the protein or
the functional ligand. By controlling the concentration of the
modulator molecule, and thus the percent saturation of the
regulatory site, the functional activity of an allosterically regu-
lated protein can be increased or decreased.
We have spoken thus far only of interactions between
regulatory and functional binding sites. There is, however,
a way that functional sites can infl uence each other in certain
proteins. These proteins are composed of more than one poly-
peptide chain held together by electrical attractions between the
chains. There may be only one binding site, a functional binding
site, on each chain. The binding of a functional ligand to one
of the chains, however, can result in an alteration of the func-
tional binding sites in the other chains. This happens because
the change in shape of the chain that holds the bound ligand
induces a change in the shape of the other chains. The interac-
tion between the functional binding sites of a multimeric (more
than one polypeptide chain) protein is known as
cooperativity.
It can result in a progressive increase in the affi nity for ligand
binding as more and more of the sites become occupied. Such a
Protein Y
Ligand
Protein X
Protein X
(low-affinity
binding site)
Protein Y
(high-affinity
binding site)
100
75
50
25
0
Ligand concentration
Percent saturation
50% bound
25% bound
Figure 3–31
When two different proteins, X and Y, are able to bind the same
ligand, the protein with the higher-affi nity binding site (protein Y)
has more bound sites at any given ligand concentration up to 100
percent saturation.
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