CASE FILES: BIOCHEMISTRY
(HbS), leading to sickle cell anemia, is a classic example of mutations that
affect protein structure.
Protein structure is typically classified as consisting of four levels:
sequence of amino acids
in the protein.
local three-dimensional spatial arrangement of amino acids that are
close to one another
in the primary sequence.
a-Helices and b-sheets
pose the majority of secondary structures in all known proteins.
spatial arrangement of amino acid residues that are far
in the linear primary sequence of a single polypeptide chain, and it
These noncovalent forces
which is also the primary stabilization force for
the formation of a-helices and P-sheets,
electrostatic interactions, van der
hydrophobic effects. Quaternary structure
is the manner
subunits of a multi-subunit protein are arranged
with respect to
hemoglobin has four subunits called globins.
two a (a1 and a2) and two b (b1 and b2) globin chains.
Each globin chain
has an associated heme prosthetic group, which is the site of oxygen binding
and release. All globin chains have similar primary sequences. The secondary
structure of globin chains consists of approximately
similar primary sequence promotes a similar tertiary structure in all globins
that is called the
which is compact and globular in overall con-
quaternary structure of HbA can be described as a dimer
of a 1b1 and a2a2 dimers.
The aP dimers move relative to one another during
the binding and release of oxygen.
Hemoglobin must remain soluble
at high concentrations within the red
blood cell to support normal oxygen binding and release properties. This is made
possible by a distribution of
amino acid side chains
residues are sequestered in the interior core
of the folded globin subunits,
of the globin
fold. The disk-shaped heme prosthetic group is inserted into a hydrophobic
pocket formed by the globin.
Hemoglobin, and the homologous monomeric protein myoglobin (Mb),
both bind and release oxygen as a function of the surrounding concentration,
or partial pressure of oxygen. A plot of percent saturation of Hb or Mb with
oxygen versus the partial pressure of oxygen is called the oxygen dissociation
curve. Unlike Mb, which has a simple hyperbolic
oxygen dissociation curve
typical of ligand binding to a monomeric protein, the
allows it to bind oxygen with
oxygen dissociation curve (Figure 1-1). Essentially, binding of oxygen