Essential Cell Biology 5th edition

130 CHAPTER 4 Protein Structure and Function
(A) normal protein can, on occasion, adopt
an abnormal, misfolded prion form
normal
protein
(B)
heterodimer
amyloid fibril
abnormal prion form
of protein
the prion form of the protein can bind
to the normal form, inducing conversion
to the abnormal conformation
binding
conversion of normal
protein to abnormal
prion form
(C) abnormal prion proteins propagate
and aggregate to form amyloid fibrils
Figure 4−19 Prion diseases are caused by proteins whose
misfolding is infectious. (A) A protein undergoes a rare
conformational change to produce an abnormally folded prion form.
(B) The abnormal form causes the conversion of normal proteins
in the host’s brain into the misfolded prion form. (C) The prions
aggregate into amyloid fibrils, which can disrupt brain-cell function,
causing a neurodegenerative disorder (see also Figure 4–18). Some
of the abnormal amyloid fibrils that form in major neurodegenerative
disorders such as Alzheimer’s disease may be able to propagate from
cell to cell in this way.
Studies of the conformation, function, and evolution of proteins have
also revealed the importance of a level of organization distinct from
the four just described. This organizational unit is the protein domain,
which is defined as any segment of a polypeptide chain that can fold
independently into a compact, stable structure. A protein domain usually
contains between 40 and 350 amino acids—folded into α helices and
β sheets and other elements of structure—and it is the modular unit from
which many larger proteins are constructed (Figure 4−20).
Different domains of a protein are often associated with different functions.
For example, the bacterial catabolite activator protein (CAP),
illustrated in Figure 4−20, has two domains: a small domain that binds
to DNA and a large domain that binds cyclic AMP, a small intracellular
signaling molecule. When the large domain binds cyclic AMP, it causes a
conformational change in the protein that enables the small domain to
bind to a specific DNA sequence and thereby promote the expression of
an adjacent gene. To provide a sense of the many different domain structures
observed in proteins, ribbon models of three different domains are
shown in Figure 4−21.
Proteins Also Contain Unstructured Regions
Small protein molecules, such as the oxygen-carrying muscle protein
myoglobin, contain only a single domain (see Figure 4−10). Larger proteins
can contain as many as several dozen domains, which are often
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Figure 4−20 Many proteins are composed
of separate functional domains. Elements
of secondary structure such as α helices
and β sheets pack together into stable,
independently folding, globular elements
called protein domains. A typical protein
molecule is built from one or more domains,
linked by a region of polypeptide chain
that is often relatively unstructured. The
ribbon diagram on the right represents the
bacterial transcription regulatory protein
CAP, which consists of one large cyclic
AMP-binding domain (outlined in blue) and
one small DNA-binding domain (outlined
in yellow). The function of this protein is
described in Chapter 8 (see Figure 8−9).
α helix
β sheet
secondary
structure
single protein
domain
protein molecule
made of two
different domains