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

114 Chapter 3: Proteins
nonpolar
side chains
unfolded polypeptide
polar
side
chains
polypeptide
backbone
Figure 3–5 How a protein folds into a
compact conformation. The polar amino
acid side chains tend to lie on the outside
of the protein, where they can interact with
water; the nonpolar amino acid side chains
are buried on the inside forming a tightly
packed hydrophobic core of atoms that
are hidden from water. In this schematic
drawing, the protein contains only about
35 amino acids.
polar side chain on the
outside of the molecule
can form hydrogen
bonds to water
hydrophobic core region
contains nonpolar
side chains
folded conformation in aqueous environment
the distribution of its polar and nonpolar amino acids. The nonpolar (hydrophobic)
side chains in a protein—belonging to such amino acids as phenylalanine,
leucine, valine, and tryptophan—tend MBoC6 m3.05/3.05to cluster in the interior of the molecule
(just as hydrophobic oil droplets coalesce in water to form one large droplet). This
enables them to avoid contact with the water that surrounds them inside a cell.
In contrast, polar groups—such as those belonging to arginine, glutamine, and
histidine—tend to arrange themselves near the outside of the molecule, where
they can form hydrogen bonds with water and with other polar molecules (Figure
3–5). Polar amino acids buried within the protein are usually hydrogen-bonded to
other polar amino acids or to the polypeptide backbone.
Proteins Fold into a Conformation of Lowest Energy
As a result of all of these interactions, most proteins have a particular three-dimensional
structure, which is determined by the order of the amino acids in its
chain. The final folded structure, or conformation, of any polypeptide chain is
generally the one that minimizes its free energy. Biologists have studied protein
folding in a test tube using highly purified proteins. Treatment with certain
solvents, which disrupt the noncovalent interactions holding the folded chain
together, unfolds, or denatures, a protein. This treatment converts the protein into
a flexible polypeptide chain that has lost its natural shape. When the denaturing
solvent is removed, the protein often refolds spontaneously, or renatures, into its
original conformation. This indicates that the amino acid sequence contains all of
the information needed for specifying the three-dimensional shape of a protein, a
critical point for understanding cell biology.
Most proteins fold up into a single stable conformation. However, this conformation
changes slightly when the protein interacts with other molecules in the
cell. This change in shape is often crucial to the function of the protein, as we see
later.
Although a protein chain can fold into its correct conformation without outside
help, in a living cell special proteins called molecular chaperones often assist
in protein folding. Molecular chaperones bind to partly folded polypeptide chains
and help them progress along the most energetically favorable folding pathway. In
the crowded conditions of the cytoplasm, chaperones are required to prevent the
temporarily exposed hydrophobic regions in newly synthesized protein chains
from associating with each other to form protein aggregates (see p. 355). However,
the final three-dimensional shape of the protein is still specified by its amino acid
sequence: chaperones simply make reaching the folded state more reliable.