Essential Cell Biology 5th edition

The Shape and Structure of Proteins
123
purified protein
isolated from cells
EXPOSE TO A HIGH
CONCENTRATION
OF UREA
denatured protein
REMOVE
UREA
protein refolds into its
original conformation
Figure 4–7 Denatured proteins can
often recover their natural shapes. This
type of experiment demonstrates that the
conformation of a protein is determined
solely by its amino acid sequence.
Renaturation requires the correct conditions
and works best for small proteins.
Protein folding has been studied in the laboratory using highly purified
proteins. A protein can be unfolded, or denatured, by treatment with solvents
that disrupt the noncovalent interactions holding the folded chain
together. This treatment converts the protein into a flexible polypeptide
chain that has lost its natural shape. Under the right conditions, when the
denaturing solvent is removed, the protein often refolds spontaneously
into its original conformation—a ECB5 process 04.07 called renaturation (Figure 4–7).
The fact that a denatured protein can, on its own, refold into the correct
conformation indicates that all the information necessary to specify
the three-dimensional shape of a protein is contained in its amino acid
sequence.
Although a protein chain can fold into its correct conformation without
outside help, protein folding in a living cell is generally assisted by a large
set of special proteins called chaperone proteins. Some of these chaperones
bind to partly folded chains and help them to fold along the most
energetically favorable pathway (Figure 4–8). Others form “isolation
chambers” in which single polypeptide chains can fold without the risk of
forming aggregates in the crowded conditions of the cytoplasm (Figure
4–9). In either case, the final three-dimensional shape of the protein is
still specified by its amino acid sequence; chaperones merely make the
folding process more efficient and reliable.
Each protein normally folds into a single, stable conformation. This conformation,
however, often changes slightly when the protein interacts
with other molecules in the cell. Such changes in shape are crucial to the
function of the protein, as we discuss later.
QUESTION 4–1
Urea, used in the experiment shown
in Figure 4−7, is a molecule that
disrupts the hydrogen-bonded
network of water molecules. Why
might high concentrations of urea
unfold proteins? The structure of
urea is shown here.
O
C
H 2 N NH 2
ECB4 Q4.01/Q4.01
newly synthesized,
partially folded protein
chaperone
proteins
incorrectly folded
protein
correctly folded
protein
Figure 4–8 Chaperone proteins can guide the folding of a newly synthesized
polypeptide chain. The chaperones bind to newly synthesized or partially folded
chains and help them to fold along the most energetically favorable pathway. The
function of these chaperones requires ATP binding and hydrolysis.
ECB5 04.08