Essential Cell Biology 5th edition

132 CHAPTER 4 Protein Structure and Function
QUESTION 4–3
Random mutations only very rarely
result in changes that improve a
protein’s usefulness for the cell, yet
useful mutations are selected in
evolution. Because these changes
are so rare, for each useful mutation
there are innumerable mutations
that lead to either no improvement
or inactive proteins. Why, then, do
cells not contain millions of proteins
that are of no use?
structures of the DNA-binding domains of some transcription regulators
from yeast, animals, and plants are almost completely superimposable,
even though the organisms are separated by more than a billion years
of evolution. Other proteins, however, have changed their structure and
function over evolutionary time, as we now discuss.
Proteins Can Be Classified into Families
Once a protein has evolved a stable conformation with useful properties,
its structure can be modified over time to enable it to perform new functions.
We know that this occurred quite often during evolution, because
many present-day proteins can be grouped into protein families, in which
each family member has an amino acid sequence and a three-dimensional
conformation that closely resemble those of the other family members.
Consider, for example, the serine proteases, a family of protein-cleaving
(proteolytic) enzymes that includes the digestive enzymes chymotrypsin,
trypsin, and elastase, as well as several proteases involved in blood clotting.
When any two of these enzymes are compared, portions of their
amino acid sequences are found to be nearly the same. The similarity
of their three-dimensional conformations is even more striking: most of
the detailed twists and turns in their polypeptide chains, which are several
hundred amino acids long, are virtually identical (Figure 4−22). The
various serine proteases nevertheless have distinct enzymatic activities,
each cleaving different proteins or the peptide bonds between different
types of amino acids.
Large Protein Molecules Often Contain More than
One Polypeptide Chain
The same type of weak noncovalent bonds that enable a polypeptide
chain to fold into a specific conformation also allow proteins to bind
to each other to produce larger structures in the cell. Any region on a
protein’s surface that interacts with another molecule through sets of
noncovalent bonds is termed a binding site. A protein can contain binding
sites for a variety of molecules, large and small. If a binding site recognizes
the surface of a second protein, the tight binding of two folded
polypeptide chains at this site will create a larger protein, whose quaternary
structure has a precisely defined geometry. Each polypeptide chain
in such a protein is called a subunit, and each of these subunits may
contain more than one domain.
Figure 4−22 Serine proteases constitute a
family of proteolytic enzymes. Backbone
models of two serine proteases, elastase
and chymotrypsin, are illustrated. Although
only those amino acid sequences in the
polypeptide chain shaded in green are
the same in the two proteins, the two
conformations are very similar nearly
everywhere. Nonetheless, the two proteases
act on different substrates.
The active site of each enzyme—where
its substrates are bound and cleaved—is
circled in red. The amino acid serine directly
participates in the cleavage reaction,
which is why the enzymes are called serine
proteases. The black dots on the right side
of the chymotrypsin molecule mark the two
ends created where the enzyme has cleaved
its own backbone.
HOOC
elastase
HOOC
NH 2
NH 2
chymotrypsin