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

118 Chapter 3: Proteins
SH3 domain
ATP
Figure 3–10 A protein formed from
multiple domains. In the Src protein
shown, a C-terminal domain with two lobes
(yellow and orange) forms a protein kinase
enzyme, while the SH2 and SH3 domains
perform regulatory functions. (A) A ribbon
model, with ATP substrate in red. (B) A
space-filling model, with ATP substrate in
red. Note that the site that binds ATP is
positioned at the interface of the two lobes
that form the kinase. The structure of the
SH2 domain was illustrated in Figure 3–6.
(PDB code: 2SRC.)
(A)
SH2 domain
(B)
is considered to have three domains: the SH2 and SH3 domains have regulatory
roles, while the C-terminal domain is responsible for the kinase catalytic activity.
Later in the chapter, we shall return to this protein, in order to explain how proteins
can form molecular switches that transmit information throughout cells.
Figure 3–11 presents ribbon models of three differently organized protein
domains. As these examples illustrate, the central core of a domain can be constructed
from α helices, from β sheets, or from various combinations of these two
fundamental folding elements.
The smallest protein molecules
MBoC6
contain
m3.10/3.10
only a single domain, whereas larger
proteins can contain several dozen domains, often connected to each other by
short, relatively unstructured lengths of polypeptide chain that can act as flexible
hinges between domains.
Few of the Many Possible Polypeptide Chains Will Be Useful
to Cells
Since each of the 20 amino acids is chemically distinct and each can, in principle,
occur at any position in a protein chain, there are 20 × 20 × 20 × 20 = 160,000
different possible polypeptide chains four amino acids long, or 20 n different possible
polypeptide chains n amino acids long. For a typical protein length of about
300 amino acids, a cell could theoretically make more than 10 390 (20 300 ) different
polypeptide chains. This is such an enormous number that to produce just one
molecule of each kind would require many more atoms than exist in the universe.
Only a very small fraction of this vast set of conceivable polypeptide chains
would adopt a stable three-dimensional conformation—by some estimates, less
(A) (B) (C)
Figure 3–11 Ribbon models of three
different protein domains. (A) Cytochrome
b 562 , a single-domain protein involved in
electron transport in mitochondria. This
protein is composed almost entirely of
α helices. (B) The NAD-binding domain of
the enzyme lactic dehydrogenase, which
is composed of a mixture of α helices and
parallel β sheets. (C) The variable domain
of an immunoglobulin (antibody) light
chain, 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 denoted by red
arrows. Note how the polypeptide chain
generally traverses back and forth across
the entire domain, making sharp turns only
at the protein surface (Movie 3.5). It is the
protruding loop regions (yellow) that often
form the binding sites for other molecules.
(Adapted from drawings courtesy of Jane
Richardson.)