4 Three-Dimensional Structure of Proteins
The /3-pleated sheet occurs as a principal secondary
structure in proteins found in persons with
The generic name /
has been suggested for this
group of disorders. The proteins that accumulate are called
amyloid and are aggregates of twisted
-pleated sheet
fibrils. They derive from endogenous proteins (e.g., im-
munoglobulins) on selective proteolysis and other chem-
ical modifications. The fibrillar proteins are insoluble
and relatively inert to proteolysis. Their accumulation in
tissues and organs can severely disrupt normal physio-
logical processes. The amyloid deposit, which occurs in
several different tissues, is produced in certain chronic in-
flammatory diseases, in some cancers, and in the brain with
some disorders, e.g.,
Alzheimer’s disease.
Partial or total
disappearance of amyloid deposits in mice has been noted
on administration of dimethyl sulfoxide, which disrupts
hydrogen bonds.
yS-Tums which are stabilized by a hydrogen bond, cause
polypeptide chains to be compact molecules (e.g., glob-
ular proteins of spherical or ellipsoidal shape). The four
amino acid residues of a //-turn form a hairpin structure in
a polypeptide chain, thus providing an energetically eco-
nomical and space-saving method of turning a corner. Two
tetrapeptide conformations can accomplish a /3-turn that
is stabilized by a hydrogen bond (Figure 4-7).
Two forms of /S-tums. Each is a tetrapeptide and accomplishes a hairpin
turn. The amino acid residues are identified by numbering the a-carbons
1-4. The CO group of residue 1 is hydrogen-bonded to the NH group of
residue 4. Structure (b) is stable only if a glycine (R = H) residue is present
as the third residue because of steric hindrance between the R-group and
the carbonyl oxygen (double-headed arrow).
Random Coil
Certain regions of peptides may not possess any defin-
able repeat pattern in which each residue of the peptide
chain interacts with other residues, as in an a-helix. How-
ever, a given amino acid sequence has only one con-
formation, or possibly a few, into which it coils itself.
This conformation has minimal energy. Since energy is
required to bring about change in protein conformation,
the molecule may remain trapped in a conformation cor-
responding to minimal energy, even though it is not at
absolute minimum internal energy. This concept of a
molecule seeking a preferred, low-energy state is the ba-
sis for the tenet that the primary amino acid sequence of
proteins determines the secondary, tertiary, and quaternary
Determination of Secondary Structure by Using
Circular Dichroism (CD) Spectroscopy
Circular dichroism (CD) spectroscopy is widely used to
determine the amount of a-helix, //-pleated sheet, and ran-
dom coil structures in a protein molecule. The principle
of CD is based on the fact that asymmetrical structures
absorb light in an asymmetrical manner. Natural light vi-
brates in all planes perpendicular to its direction of travel;
but its plane of polarization can be fixed to possess either
left or right orientation. However, in circular polarization
the direction of polarization rotates with the frequency of
the light. If the rotation is
it is called
cularly polarized light and if
it is called
circularly polarized light.
Absorption of light by a given molecule is equal to
x C, where
is the molar extinction coefficient and C
is the molar concentration. Asymmetrical molecules ab-
sorb right or left circularly polarized light differently. This
difference in absorption
£r — Sr
is called
molar ellipticity,
which is dependent upon the wavelength of the incident
light. A plot
oi ei — £r
versus the wavelength provides a
CD spectrum characteristic of different secondary struc-
tures (Figure 4-8).
Other Types of Secondary Structure
Other distinct types of protein secondary structure include
the type present in collagen, a fibrous connective tissue
protein and the most abundant of all human proteins. Col-
lagen peptide chains are twisted together into a three-
stranded helix. The resultant “three-stranded rope” is then
twisted into a
(Chapter 10).
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