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

138 Chapter 3: Proteins
heavy chain
V H
V H
hypervariable loops
S
S
C H 1 C H 1
S S
NH 2
S
S S
S
S
V L
C L
V L
S
S
S
S S
S
S
S S
S S
S
S
S
S
C L
C H 2
S
S
S
S
C H 2
disulfide
bond
variable domain
of light chain (V L )
(A)
C H 3
S
S
Antibody Binding Sites Are Especially Versatile
S
S
C H 3
All proteins must bind to particular ligands to carry out their various functions.
The antibody family is notable for its capacity for tight, highly selective binding
(discussed in detail in Chapter 24).
Antibodies, or immunoglobulins, are proteins produced by the immune system
in response to foreign molecules, such as those on the surface of an invading
microorganism. Each antibody binds tightly to a particular target molecule,
thereby either inactivating the target molecule directly or marking it for destruction.
An antibody recognizes its target (called an antigen) with remarkable specificity.
Because there are potentially billions of different antigens that humans
might encounter, we have to be able to produce billions of different antibodies.
Antibodies are Y-shaped molecules with two identical binding sites that are
complementary to a small portion of the surface of the antigen molecule. A
detailed examination of the antigen-binding sites of antibodies reveals that they
are formed from several loops of polypeptide
MBoC6
chain
m25.32/24.28
that protrude from the ends
of a pair of closely juxtaposed protein domains (Figure 3–42). Different antibodies
generate an enormous diversity of antigen-binding sites by changing only the
length and amino acid sequence of these loops, without altering the basic protein
structure.
Loops of this kind are ideal for grasping other molecules. They allow a large
number of chemical groups to surround a ligand so that the protein can link to it
with many weak bonds. For this reason, loops often form the ligand-binding sites
in proteins.
(B)
COOH
constant domain
of light chain (C L )
Figure 3–42 An antibody molecule.
A typical antibody molecule is Y-shaped
and has two identical binding sites for
its antigen, one on each arm of the Y. As
explained in Chapter 24, the protein is
composed of four polypeptide chains (two
identical heavy chains and two identical
and smaller light chains) held together
by disulfide bonds. Each chain is made
up of several different immunoglobulin
domains, here shaded either blue or gray.
The antigen-binding site is formed where
a heavy-chain variable domain (V H ) and
a light-chain variable domain (V L ) come
close together. These are the domains that
differ most in their sequence and structure
in different antibodies. At the end of each
of the two arms of the antibody molecule,
these two domains form loops that bind to
the antigen (see Movie 24.5).
The Equilibrium Constant Measures Binding Strength
Molecules in the cell encounter each other very frequently because of their continual
random thermal movements. Colliding molecules with poorly matching
surfaces form few noncovalent bonds with one another, and the two molecules
dissociate as rapidly as they come together. At the other extreme, when many
noncovalent bonds form between two colliding molecules, the association can
persist for a very long time (Figure 3–43). Strong interactions occur in cells whenever
a biological function requires that molecules remain associated for a long
time—for example, when a group of RNA and protein molecules come together to
make a subcellular structure such as a ribosome.