Essential Cell Biology 5th edition

The Shape and Structure of Proteins
121
glutamic acid
N
H
H
C
O
C
electrostatic
attractions
+
R
CH 2
CH 2
CH 2
O
C
H
H
O
N
+
H
CH 2
CH 2
van der Waals attractions
hydrogen bond
O
C
R
H
C
C
H
O
H
N
C
O
C
H
N
R
H
C
CH 2
C H
C
N
O H
lysine
CH3 CH 3
H C
C
CH 3
CH C 3
H
H
C CH N
3
N
H C H
C
C C N O
H
O
H
valine
alanine
O
H
valine
Figure 4–4 Three types of noncovalent
bonds help proteins fold. Although a
single one of any of these bonds is quite
weak, many of them together can create a
strong bonding arrangement that stabilizes
a particular three-dimensional structure,
as in the small polypeptide shown in
the center. R is often used as a general
designation for an amino acid side chain.
Protein folding is also aided by hydrophobic
forces, as shown in Figure 4–5.
enormous number of ways. The shape of each of these folded chains,
however, is constrained by many sets of weak noncovalent bonds that
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form within proteins. These bonds involve atoms in the polypeptide
backbone, as well as atoms within the amino acid side chains. The noncovalent
bonds that help proteins fold up and maintain their shape include
hydrogen bonds, electrostatic attractions, and van der Waals attractions,
which are described in Chapter 2 (see Panel 2–3, pp. 70–71). Because a
noncovalent bond is much weaker than a covalent bond, it takes many
noncovalent bonds to hold two regions of a polypeptide chain tightly
together. The stability of each folded shape is largely determined by the
combined strength of large numbers of noncovalent bonds (Figure 4–4).
A fourth weak interaction, the hydrophobic force, also has a central role
in determining the shape of a protein. In an aqueous environment, hydrophobic
molecules, including the nonpolar side chains of particular amino
acids, tend to be forced together to minimize their disruptive effect on
the hydrogen-bonded network of the surrounding water molecules (see
Panel 2−3, pp. 70–71). Therefore, an important factor governing the folding
of any protein is the distribution of its polar and nonpolar amino
acids. The nonpolar (hydrophobic) side chains—which belong to amino
acids such as phenylalanine, leucine, valine, and tryptophan (see Figure
4–3)—tend to cluster in the interior of the folded protein (just as hydrophobic
oil droplets coalesce to form one large drop). Tucked away inside
the folded protein, hydrophobic side chains can avoid contact with the
aqueous environment that surrounds them inside a cell. In contrast, polar
side chains—such as those belonging to arginine, glutamine, and histidine—tend
to arrange themselves near the outside of the folded protein,
where they can form hydrogen bonds with water and with other polar
molecules (Figure 4–5). When polar amino acids are buried within the
protein, they are usually hydrogen-bonded to other polar amino acids or
to the polypeptide backbone (Figure 4–6).