58
chapter 4
Three-Dimensional Structure of Proteins
Triose phosphate isomerase
FIGURE 4-10
The a/5-barrel structure seen in triose phosphate isomerase. This structure
consists of eight /i-pleated sheets (represented by arrows) arranged in a
cylindrical manner and surrounded by eight a-helices. (Reproduced with
permission from J.S. Richardson.)
Membrane proteins tend to be rich in hydrophobic amino
acids that facilitate their noncovalent interaction with
membrane lipids. In both large globular and membrane
proteins, the ratio of aqueous solvent-exposed surface to
volume is small; hence, the need for polar, ionic, and hy-
drogen bonding groups is minimized, whereas the need
for hydrophobic interaction is maximized. Small globular
proteins tend to have more S-S bonds, which contribute
significantly to tertiary structure stability, than do large
globular proteins. These S-S bonds may be critical for
proteins that lack sufficient stabilization from hydrophobic
interactions.
Hydrophobic interactions are considered to be a ma-
jor determinant in the maintenance of protein conforma-
tion. Hydrophobic interactions are due to the tendency of
nonpolar side chains to interact with other nonpolar side
chains rather than with water. Such interactions may in-
volve the side chains of different adjacent molecules, or
they may occur between side chains on the same protein
molecule.
Nonpolar
side
chains
are
not
attracted
to
water
molecules either ionically or through hydrogen bonds
(van der Waals attractions do occur). When hydrophobic
molecules are put into an aqueous solution, they disturb
the stable hydrogen-bonded water structure. To minimize
this disturbance (and to return to the lowest possible free-
energy state), the hydrophobic groups clump together as
much as possible, so that the surface-to-volume ratio of
the hydrophobic material is minimal. Once the chains are
brought close together, van der Waals attractive forces can
assist in holding them there. The van der Waals forces
are weak, however, and most of the “hydrophobic bond
energy” probably is from the free energy made available
when water is able to self-associate in a stable structure
instead of solvating all the hydrophobic groups in an unsta-
ble array. The driving force for the reaggregation of water
in the presence of hydrophobic material can be envisioned
in two ways:
1. The water surrounding a hydrophobic group is
ice-like (highly ordered) because of limitations
imposed on its movement by the presence of the
hydrophobic material. A decrease in hydrophobic
surface area causes a decrease in order and hence an
increase in entropy that helps lower the free energy of
the solution.
2. Hydrophobic regions in an aqueous solution break up
hydrogen bond networks. A decrease in the area of the
hydrophobic surface permits more hydrogen bonds to
form, thus lowering the free energy of the solution.
4.5 Quaternary Structure
Quaternary structure exists in proteins consisting of two or
more identical or different polypeptide chains
(subunits).
These proteins are called
oligomers
because they have two
or more subunits. The quaternary structure describes the
manner in which subunits are arranged in the native pro-
tein. Subunits are held together by noncovalent forces; as
a result, oligomeric proteins can undergo rapid conforma-
tional changes that affect biological activity. Oligomeric
proteins include the hemoglobins (Chapter 28), allosteric
enzymes (Chapter 7) responsible for the regulation of
metabolism, and contractile proteins such as actin and
tubulin (Chapter 21).
4.6 Dénaturation
Dénaturation of a native protein may be described as a
change in its physical, chemical, or biological properties.
Mild dénaturation may disrupt tertiary or quaternary struc-
tures, whereas harsher conditions may fragment the chain.
Mild dénaturation normally is a reversible process. Some
