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

THE SHAPE AND STRUCTURE OF PROTEINS
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than one in a billion. And yet the majority of proteins present in cells do adopt
unique and stable conformations. How is this possible? The answer lies in natural
selection. A protein with an unpredictably variable structure and biochemical
activity is unlikely to help the survival of a cell that contains it. Such proteins would
therefore have been eliminated by natural selection through the enormously long
trial-and-error process that underlies biological evolution.
Because evolution has selected for protein function in living organisms, the
amino acid sequence of most present-day proteins is such that a single conformation
is stable. In addition, this conformation has its chemical properties finely
tuned to enable the protein to perform a particular catalytic or structural function
in the cell. Proteins are so precisely built that the change of even a few atoms in
one amino acid can sometimes disrupt the structure of the whole molecule so
severely that all function is lost. And, as discussed later in this chapter, when certain
rare protein misfolding accidents occur, the results can be disastrous for the
organisms that contain them.
Proteins Can Be Classified into Many Families
Once a protein had evolved that folded up into a stable conformation with useful
properties, its structure could be modified during evolution to enable it to
perform new functions. This process has been greatly accelerated by genetic
mechanisms that occasionally duplicate genes, allowing one gene copy to evolve
independently to perform a new function (discussed in Chapter 4). This type of
event has occurred very often in the past; as a result, many present-day proteins
can be grouped into protein families, each family member having an amino acid
sequence and a three-dimensional conformation that resemble those of the other
family members.
Consider, for example, the serine proteases, a large family of protein-cleaving
(proteolytic) enzymes that includes the digestive enzymes chymotrypsin, trypsin,
and elastase, and several proteases involved in blood clotting. When the protease
portions of any two of these enzymes are compared, parts of their amino acid
sequences are found to match. 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 3–12). The many different serine proteases nevertheless have
distinct enzymatic activities, each cleaving different proteins or the peptide bonds
between different types of amino acids. Each therefore performs a distinct function
in an organism.
The story we have told for the serine proteases could be repeated for hundreds
of other protein families. In general, the structure of the different members of a
HOOC
elastase
HOOC
NH 2
NH 2
chymotrypsin
Figure 3–12 A comparison of the
conformations of two serine proteases.
The backbone conformations of elastase
and chymotrypsin. Although only those
amino acids in the polypeptide chain
shaded in green are the same in the two
proteins, the two conformations are very
similar nearly everywhere. The active site of
each enzyme is circled in red; this is where
the peptide bonds of the proteins that
serve as substrates are bound and cleaved
by hydrolysis. The serine proteases derive
their name from the amino acid serine,
whose side chain is part of the active site
of each enzyme and directly participates
in the cleavage reaction. The two dots on
the right side of the chymotrypsin molecule
mark the new ends created when this
enzyme cuts its own backbone.