The linear sequence of amino acids in a protein is the primary structure of the protein.
In proteins, adjacent amino acids are joined covalently by peptide bonds, which are amide linkages
between the α-carboxyl group of one amino acid and the α-amino group of the next amino acid.
Peptide bond characteristics: The peptide bond has a partial double-bond character; that is, it is shorter
than a single bond and is rigid and planar (Fig. 2.2B). This prevents free rotation around the bond
between the carbonyl carbon and the nitrogen of the peptide bond. However, the bonds between the α-
carbons and the α-amino or α-carboxyl groups can rotate freely (although they are limited by the size
and character of the Rgroups). This allows the polypeptide chain to assume a variety of possible
conformations. The peptide bond is almost always in the trans configuration (instead of the cis; see Fig.
2.2B), largely because of steric interference of the R groups (side chains) when in the cis position.
Peptide bond polarity: Like all amide linkages, the −C = O and −NH groups of the peptide bond are
uncharged, and neither accept nor release protons over the pH range of 2 to 12. The charged groups
present in polypeptides consist solely of the N-terminal (α-amino) group, the C-terminal (α-carboxyl)
group, and any ionized groups present in the side chains of the constituent amino acids. However, the
−C = O and −NH groups of the peptide bond are polar, and are involved in hydrogen bonds (e.g., in α-
helices and β-sheets), as described on page 17.
Α-Helix
Rigid, right-handed spiral structure, consisting of a tightly packed, coiled polypeptide backbone core,
with the side chains of the component L-amino acids extending outward from the central axis to avoid
interfering sterically with each other Hydrogen bonds: An α-helix is stabilized by extensive hydrogen
bonding between the peptide bond carbonyl oxygens and amide hydrogens that are part of the
polypeptide backbone (see Fig. 2.6). The hydrogen bonds extend up and are parallel to the spiral from
the carbonyl oxygen of one peptide bond to the –NH group of a peptide linkage four residues ahead in
the polypeptide. This ensures that all but the first and last peptide bond components are linked to each
other through intrachain hydrogen bonds.
Amino acids per turn: Each turn of an α-helix contains 3.6 amino acids. Thus, amino acids spaced three
or four residues apart in the primary sequence are spatially close together when folded in the α-helix.
Amino acids that disrupt an α-helix: The R group of an amino acid determines its propensity to be in an
α-helix. Proline disrupts an α-helix because its rigid secondary amino group is not geometrically
compatible with the right-handed spiral of the α-helix. Instead, it inserts a kink in the chain, which
interferes with the smooth, helical structure. Glycine, with hydrogen as its R group, confers high
flexibility. Additionally, amino acids with charged or bulky R groups, such as glutamate and tryptophan,
respectively those with a branch at the β-carbon, the first carbon in the R group (e.g., valine), are less
likely to be found in an α-helix.
Β-Sheet
The β-sheet is another form of secondary structure in which all of the peptide bond components are
involved in hydrogen bonding (Fig. 2.7A). Because the surfaces of β-sheets appear to be folded or to
form “pleats,” they are often called β-pleated sheets. Pleating results from successive α-carbons being
slightly above or below the plane of the sheet. Illustrations of protein structure often show β-strands as
broad arrows (Fig. 2.7B).
Formation: A β-sheet is formed by two or more peptide chains (β-strands) aligned laterally and stabilized
by hydrogen bonds between the carboxyl and amino groups of amino acids that either are far apart in a
single polypeptide
(intrachain bonds) or are in different polypeptide chains (interchain bonds). The adjacent β-strands are
arranged either antiparallel to each other (with the N-termini alternating as shown in Fig. 2.7B) or
parallel to each other (with the N-termini together as shown in Fig. 2.7C). On each β-strand, the R
groups of adjacent amino acids extend in opposite directions, above and below the plane of the β-sheet.
Β-sheets are not flat and have a right-handed curl (twist) when viewed along the polypeptide backbone.
Comparing α-helices and β-sheets: In β-sheets, the β-strands are almost fully extended and the
hydrogen bonds between the strands are perpendicular to the polypeptide backbone (see Fig. 2.7A). In
contrast, in α-helices, the polypeptide is coiled and the hydrogen bonds are parallel to the backbone
(see Fig. 2.6).
Β-Bends
Β-bends, also called reverse turns and β-turns, reverse the direction of a polypeptide chain, helping it
form a compact, globular shape. They are usually found on the surface of protein molecules and often
include charged residues. Β-bends were given this name because they often connect successive strands
of antiparallel β-sheets. They are generally composed of four amino acids, one of which may be proline,
the amino acid that causes a kink in the polypeptide chain. Glycine, the amino acid with the smallest R
group, is also frequently found in β-bends. Β-bends are stabilized by the formation of hydrogen bonds
between the first and last residues in the bend.
Supersecondary structures (motifs)
Globular proteins are constructed by combining secondary structural elements including α-helices, β-
sheets, and coils, producing specific geometric patterns, or motifs. These form primarily the core
(interior) region of the molecule. They are connected by loop regions (e.g., β-bends) at the surface of
the protein. Supersecondary structures are usually produced by the close packing of side chains from
adjacent secondary structural elements. For example, α-helices and β-sheets that are adjacent in the
amino acid sequence are also usually (but not always) adjacent in the final, folded protein. Some of the
more common motifs are illustrated in Figure 2.8.
