Essential Cell Biology 5th edition

The Shape and Structure of Proteins
129
β Sheets Form Rigid Structures at the Core of Many
Proteins
A β sheet is made when hydrogen bonds form between segments of a
polypeptide chain that lie side by side (see Figure 4−13A). When the neighboring
segments run in the same orientation (say, from the N-terminus
to the C-terminus), the structure forms a parallel β sheet; when they
run in opposite directions, the structure forms an antiparallel β sheet
(Figure 4−17). Both types of β sheet produce a very rigid, pleated structure,
and they form the core of many proteins. Even the small bacterial
transport protein HPr (see Figure 4−11) contains several β sheets.
β sheets have remarkable properties. They give silk fibers their extraordinary
tensile strength. They also form the basis of amyloid structures, in
which β sheets are stacked together in long rows with their amino acid
side chains interdigitated like the teeth of a zipper (Figure 4−18). Such
structures play an important role in cells, as we discuss later in this chapter.
However, they can also precipitate disease, as we see next.
Misfolded Proteins Can Form Amyloid Structures
That Cause Disease
When proteins fold incorrectly, they sometimes form amyloid structures
that can damage cells and even whole tissues. These amyloid struc-tures
are thought to contribute to a number of neurodegenerative disorders, such
as Alzheimer’s disease and Huntington’s disease. Some infectious neurodegenerative
diseases—including scrapie in sheep, bovine spongiform
encephalopathy (BSE, or “mad cow” disease) in cattle, and Creutzfeldt–
Jakob disease (CJD) in humans—are caused by misfolded proteins called
prions. The misfolded prion form of a protein can convert the properly
folded version of the protein in an infected brain into the abnormal conformation.
This allows the misfolded prions to form aggregates (Figure 4−19),
which can spread rapidly from cell to cell, eventually causing the death of
the affected animal or human. Prions are considered “infectious” because
they can also spread from an affected individual to a normal individual via
contaminated food, blood, or surgical instruments, for example.
(A)
(B)
Figure 4−17 β sheets come in two
varieties. (A) Antiparallel β sheet (see also
Figure 4−13A). (B) Parallel β sheet. Both of
these structures are common in proteins.
By convention, the arrows point toward
the C-terminus of the polypeptide chain
(Movie 4.4).
ECB5 04.17
Proteins Have Several Levels of Organization
A protein’s structure does not begin and end with α helices and
β sheets. Its complete conformation includes several interdependent
levels of organization, which build one upon the next. Because a protein’s
structure begins with its amino acid sequence, this is considered its
primary structure. The next level of organization includes the α helices
and β sheets that form within certain segments of the polypeptide chain;
these folds are elements of the protein’s secondary structure. The full,
three-dimensional conformation formed by an entire polypeptide chain—
including the α helices, β sheets, and all other loops and folds that form
between the N- and C-termini—is sometimes referred to as the tertiary
structure. Finally, if the protein molecule exists as a complex of more
than one polypeptide chain, then these interacting polypeptides form its
quaternary structure.
Figure 4−18 β sheets can stack to form an amyloid structure.
(A) Electron micrograph showing an amyloid structure from a yeast.
This structure resembles the type of insoluble aggregates observed in
the neurons of individuals with different neurodegenerative diseases
(see Figure 4−19). (B) Schematic representation shows the stacking of
β sheets that stabilizes an individual amyloid strand. (A, from M.R.
Sawaya et al., Nature 447:453–457, 2007. With permission from
Macmillan Publishers Ltd.)
(A)
50 nm
(B)