Text adapted from Campbell Biology 10th Edition
Protein Structure and Function
Amino Acid Monomers
All amino acids share a common structure. An amino acid is an
organic molecule with both an amino group and a carboxyl group. The
figure at the right shows the general formula for an amino acid. At the
center of the amino acid is an asymmetric carbon atom called the
alpha (α) carbon. Its four different partners are an amino group, a
carboxyl group, a hydrogen atom, and a variable group symbolized
by R. The R group, also called the side chain, differs with each amino
acid.
The physical and chemical properties of the side chain determine the unique characteristics of a
particular amino acid, thus affecting its functional role in a polypeptide. Amino acids are grouped
according to the properties of their side chains. One group consists of amino acids with nonpolar
side chains, which are hydrophobic. Another group consists of amino acids with polar side
chains, which are hydrophilic. Acidic amino acids are those with side chains that are generally
negative in charge due to the presence of a carboxyl group, which is usually dissociated (ionized)
at cellular pH. Basic amino acids have amino groups in their side chains that are generally positive
in charge. (Notice that all amino acids have carboxyl groups and amino groups; the terms acidic
and basic in this context refer only to groups in the side
chains.) Because they are charged, acidic and basic side
chains are also hydrophilic.
Polypeptides (Amino Acid Polymers)
Now that we have examined amino acids, let’s see how
they are linked to form polymers (Figure 5.15). When
two amino acids are positioned so that the carboxyl
group of one is adjacent to the amino group of the other,
they can become joined by a dehydration reaction, with
the removal of a water molecule. The resulting covalent
bond is called a peptide bond.
Repeated over and over, this process yields a
polypeptide, a polymer of many amino acids linked by
peptide bonds. The repeating sequence of atoms
highlighted in purple in Figure 5.15 is called the
polypeptide backbone. Extending from this backbone
are the different side chains (R groups) of the amino
Text adapted from Campbell Biology 10th Edition
acids. Polypeptides range in length from a few amino acids to a thousand or more. Each specific
polypeptide has a unique linear sequence of amino acids. Note that one end of the polypeptide
chain has a free amino group, while the opposite end has a free carboxyl group. Thus, a polypeptide
of any length has a single amino end (N-terminus) and a single carboxyl end (C-terminus). In a
polypeptide of any significant size, the side chains far outnumber the terminal groups, so the
chemical nature of the molecule as a whole is determined by the kind and sequence of the side
chains. The immense variety of polypeptides in nature illustrates an important concept introduced
earlier—that cells can make many different polymers by linking a limited set of monomers into
diverse sequences.
Four Levels of Protein Structure
Most proteins have segments of their polypeptide chains repeatedly coiled or folded in patterns
that contribute to the protein’s overall shape. These coils and folds, collectively referred to as
secondary structure, are the result of hydrogen
bonds between the repeating constituents of the
polypeptide backbone (not the amino acid side
chains). Within the backbone, the oxygen atoms
have a partial negative charge, and the hydrogen
atoms attached to the nitrogens have a partial
positive charge; therefore, hydrogen bonds can
form between these atoms. Individually, these
hydrogen bonds are weak, but because there are so
many of them over a relatively long region of the
polypeptide chain, they can support a particular
shape for that part of the protein.
One such secondary structure is the 𝛂 helix, a delicate coil held together by hydrogen bonding
between every fourth amino acid, as shown above. Although each transthyretin polypeptide has
only one α helix region (see tertiary structure), other globular proteins have multiple stretches of
α helix separated by nonhelical regions (see hemoglobin on the next page). Some fibrous proteins,
such as α-keratin, the structural protein of hair, have the α helix structure over most of their length.
The other main type of secondary structure is the 𝛃 pleated sheet. As shown above, in this
structure two or more segments of the polypeptide chain lying side by side (called β strands) are
connected by hydrogen bonds between parts of the two parallel segments of the polypeptide
backbone. β pleated sheets make up the core of many globular proteins, as is the case for
transthyretin (see tertiary structure), and dominate some fibrous proteins, including the silk protein
Text adapted from Campbell Biology 10th Edition
of a spider’s web. The teamwork of so many hydrogen bonds makes each spider silk fiber stronger
than a steel strand of the same weight.
Superimposed on the patterns of secondary structure is a protein’s tertiary structure, shown above
in a ribbon model of the transthyretin polypeptide. While secondary structure involves interactions
between backbone constituents, tertiary structure is the overall shape of a polypeptide resulting
from interactions between the side chains (R groups) of the various amino acids. One type of
interaction that contributes to tertiary structure is called—somewhat misleadingly—a
hydrophobic interaction. As a polypeptide folds into its functional shape, amino acids with
hydrophobic (nonpolar) side chains usually end up in clusters at the core of the protein, out of
contact with water. Thus, a “hydrophobic interaction” is actually caused by the exclusion of
nonpolar substances by water molecules. Once nonpolar amino acid side chains are close together,
van der Waals interactions help hold them together. Meanwhile, hydrogen bonds between polar
side chains and ionic bonds between positively and negatively charged side chains also help
stabilize tertiary structure. These are all weak interactions in the aqueous cellular environment, but
their cumulative effect helps give the protein a unique shape.
Covalent bonds called disulfide bridges may further reinforce the shape of a protein. Disulfide
bridges form where two cysteine monomers, which have sulfhydryl groups (-SH) on their side
chains (see Figure 4.9), are brought close together by the folding of the protein. The sulfur of one
cysteine bonds to the sulfur of the second, and the disulfide bridge (-S-S-) rivets parts of the protein
together (see the yellow lines in Figure 5.16a). All of these different kinds of interactions can
contribute to the tertiary structure of
a protein, as shown here in a small
part of a hypothetical protein: Some
proteins consist of two or more
polypeptide chains aggregated into
one functional macromolecule.
Quaternary structure is the overall
protein structure that results from the
aggregation of these polypeptide
subunits. For example, shown above
is the complete globular transthyretin protein, made up of its four polypeptides. Another example
is collagen, shown below, which is a fibrous protein that has three identical helical polypeptides
intertwined into a larger triple helix, giving the long fibers great strength. This suits collagen fibers
to their function as the girders of connective tissue in skin, bone, tendons, ligaments, and other
body parts. (Collagen accounts for 40% of the protein in a human body.)
Text adapted from Campbell Biology 10th Edition
