Essential Cell Biology 5th edition

162 CHAPTER 4 Protein Structure and Function
the rate of selected chemical reactions. But, as we continue to learn more
about how proteins and enzymes exploit their unique conformations to
carry out their biological functions, our ability to make novel proteins
with useful functions can only improve.
family 1 family 2
(A) single-domain protein families
(B) a two-domain protein family
Figure 4−58 Most proteins belong to
structurally related families. (A) More
than two-thirds of all well-studied proteins
contain a single structural domain. The
members of these single-domain families
can have ECB5 different 04.58 amino acid sequences
but fold into a protein with a similar shape.
(B) During evolution, structural domains
have been combined in different ways to
produce families of multidomain proteins.
Almost all novelty in protein structure
comes from the way these single domains
are arranged. Unlike the number of novel
single domains, the number of multidomain
families being added to the public
databases is still rapidly increasing.
The Relatedness of Proteins Aids the Prediction of
Protein Structure and Function
Biochemists have made enormous progress over the past 150 years in
understanding the structure and function of proteins (see Table 4−2,
p. 160). These advances are the fruits of decades of painstaking research
on isolated proteins, performed by individual scientists working tirelessly
on single proteins or protein families, one by one, sometimes for their
entire careers. In the future, however, more and more of these investigations
of protein conformation and activity will likely take place on a
larger scale.
Improvements in our ability to rapidly sequence whole genomes, and
the development of methods such as mass spectrometry, have fueled
our ability to determine the amino acid sequences of enormous numbers
of proteins. Millions of unique protein sequences from thousands
of different species have thereby been deposited into publicly available
databases, and the collection is expected to double in size every
two years. Comparing the amino acid sequences of all of these proteins
reveals that the majority belong to protein families that share specific
“sequence patterns”—stretches of amino acids that fold into distinct
structural domains. In some of these families, the proteins contain only a
single structural domain. In others, the proteins include multiple domains
arranged in novel combinations (Figure 4−58).
Although the number of multidomain families is growing rapidly, the
discovery of novel single domains appears to be leveling off. This plateau
suggests that the vast majority of proteins may fold up into a limited
number of structural domains—perhaps as few as 10,000 to 20,000. For
many single-domain families, the structure of at least one family member
is known. And knowing the structure of one family member allows us
to say something about the structure of its relatives. By this account, we
have some structural information for almost three-quarters of the proteins
archived in databases (Movie 4.14).
A future goal is to acquire the ability to look at a protein’s amino acid
sequence and be able to deduce its structure and gain insight into its
function. We are coming closer to being able to predict protein structure
based on sequence information alone, but we still have a considerable
way to go. To date, computational methods that take an amino acid
sequence and search for the protein conformations with the lowest
energy have been successful for proteins less than 100 amino acids long,
or for longer proteins for which additional information is available (such
as homology with proteins whose structure is known).
Looking at an amino acid sequence and predicting how a protein will
function—alone or as part of a complex in the cell—is more challenging
still. But the closer we get to accomplishing these goals, the closer we
will be to understanding the fundamental basis of life.
ESSENTIAL CONCEPTS
• Living cells contain an enormously diverse set of protein molecules,
each made as a linear chain of amino acids linked together by covalent
peptide bonds.
• Each type of protein has a unique amino acid sequence, which