Essential Cell Biology 5th edition

The Shape and Structure of Proteins
131
Figure 4−21 Ribbon models show three
different protein domains. (A) Cytochrome
b 562 is a single-domain protein involved in
electron transfer in E. coli. It is composed
almost entirely of α helices. (B) The
NAD-binding domain of the enzyme
lactate dehydrogenase is composed of a
mixture of α helices and β sheets. (C) An
immunoglobulin domain of an antibody
molecule is composed of a sandwich of two
antiparallel β sheets. In these examples,
the α helices are shown in green, while
strands organized as β sheets are red. The
protruding loop regions (yellow) are often
unstructured and can provide binding sites
for other molecules.
(A) (B) (C)
connected by relatively short, unstructured lengths of polypeptide chain.
The ubiquity of such intrinsically disordered sequences, which continually
bend and flex due to thermal buffeting, became appreciated only
after bioinformatics methods were developed that could recognize them
from their amino acid sequences. Present estimates suggest that a third
of all eukaryotic proteins also possess longer, unstructured regions—
greater than 30 amino acids in length—in their polypeptide chains. These
unstructured sequences ECB5 can 04.21 have a variety of important functions in
cells, as we discuss later in the chapter.
Few of the Many Possible Polypeptide Chains Will Be
Useful
In theory, a vast number of different polypeptide chains could be made
from 20 different amino acids. Because each amino acid is chemically
distinct and could, in principle, occur at any position, a polypeptide chain
four amino acids long has 20 × 20 × 20 × 20 = 160,000 different possible
sequences. For a typical protein with a length of 300 amino acids, that
means that more than 20 300 (that’s 10 390 ) different polypeptide chains
could theoretically be produced. And that’s just one protein.
Of the unimaginably large collection of potential polypeptide sequences,
only a minuscule fraction is actually made by cells. That’s because most
biological functions depend on proteins with stable, well-defined threedimensional
conformations. This requirement greatly restricts the list of
polypeptide sequences present in living cells. Another constraint is that
functional proteins must be “well-behaved” and not engage in unwanted
associations with other proteins in the cell—forming insoluble protein
aggregates, for example. Many potential protein sequences would
therefore have been eliminated by natural selection through the long
trial-and-error process that underlies evolution (discussed in Chapter 9).
Thanks to natural selection, the amino acid sequences of many presentday
polypeptides have evolved to adopt a stable conformation—one that
bestows upon the protein the exact chemical properties that will enable it
to perform a particular function. Such proteins are so precisely built that
a change in even a few atoms in one amino acid can sometimes disrupt
the structure of a protein and thereby eliminate its function. In fact, the
conformations of many proteins—and their constituent domains—are so
stable and effective that they have been conserved throughout the evolution
of a diverse array of organisms. For example, the three-dimensional