Protein Denaturation and Folding
All proteins begin their existence on a ribosome as a linear
sequence of amino acid residues (Chapter 27). This
polypeptide must fold during and following synthesis to
take up its native conformation. We have seen that a native
protein conformation is only marginally stable. Modest
changes in the protein’s environment can bring about
structural changes that can affect function. We now explore
the transition that occurs between the folded and
unfolded states.
Loss of Protein Structure Results in Loss of Function
Protein structures have evolved to function in particular
cellular environments. Conditions different from those
in the cell can result in protein structural changes, large
and small. A loss of three-dimensional structure sufficient
to cause loss of function is called denaturation.
The denatured state does not necessarily equate with
complete unfolding of the protein and randomization of
conformation. Under most conditions, denatured proteins
exist in a set of partially folded states that are
poorly understood.
Most proteins can be denatured by heat, which affects
the weak interactions in a protein (primarily hydrogen
bonds) in a complex manner. If the temperature
is increased slowly, a protein’s conformation generally
remains intact until an abrupt loss of structure (and
function) occurs over a narrow temperature range (Fig.
4–26). The abruptness of the change suggests that unfolding
is a cooperative process: loss of structure in one
part of the protein destabilizes other parts. The effects
of heat on proteins are not readily predictable. The very
heat-stable proteins of thermophilic bacteria have
evolved to function at the temperature of hot springs
(~100 C). Yet the structures of these proteins often differ
only slightly from those of homologous proteins derived
from bacteria such as Escherichia coli. How these
small differences promote structural stability at high
temperatures is not yet understood.
Proteins can be denatured not only by heat but by
extremes of pH, by certain miscible organic solvents
such as alcohol or acetone, by certain solutes such as
urea and guanidine hydrochloride, or by detergents.
Each of these denaturing agents represents a relatively
mild treatment in the sense that no covalent bonds in
the polypeptide chain are broken. Organic solvents,
urea, and detergents act primarily by disrupting the hydrophobic
interactions that make up the stable core of
globular proteins; extremes of pH alter the net charge
on the protein, causing electrostatic repulsion and the
disruption of some hydrogen bonding. The denatured
states obtained with these various treatments need not
be equivalent.
All proteins begin their existence on a ribosome as a linear
sequence of amino acid residues (Chapter 27). This
polypeptide must fold during and following synthesis to
take up its native conformation. We have seen that a native
protein conformation is only marginally stable. Modest
changes in the protein’s environment can bring about
structural changes that can affect function. We now explore
the transition that occurs between the folded and
unfolded states.
Loss of Protein Structure Results in Loss of Function
Protein structures have evolved to function in particular
cellular environments. Conditions different from those
in the cell can result in protein structural changes, large
and small. A loss of three-dimensional structure sufficient
to cause loss of function is called denaturation.
The denatured state does not necessarily equate with
complete unfolding of the protein and randomization of
conformation. Under most conditions, denatured proteins
exist in a set of partially folded states that are
poorly understood.
Most proteins can be denatured by heat, which affects
the weak interactions in a protein (primarily hydrogen
bonds) in a complex manner. If the temperature
is increased slowly, a protein’s conformation generally
remains intact until an abrupt loss of structure (and
function) occurs over a narrow temperature range (Fig.
4–26). The abruptness of the change suggests that unfolding
is a cooperative process: loss of structure in one
part of the protein destabilizes other parts. The effects
of heat on proteins are not readily predictable. The very
heat-stable proteins of thermophilic bacteria have
evolved to function at the temperature of hot springs
(~100 C). Yet the structures of these proteins often differ
only slightly from those of homologous proteins derived
from bacteria such as Escherichia coli. How these
small differences promote structural stability at high
temperatures is not yet understood.
Proteins can be denatured not only by heat but by
extremes of pH, by certain miscible organic solvents
such as alcohol or acetone, by certain solutes such as
urea and guanidine hydrochloride, or by detergents.
Each of these denaturing agents represents a relatively
mild treatment in the sense that no covalent bonds in
the polypeptide chain are broken. Organic solvents,
urea, and detergents act primarily by disrupting the hydrophobic
interactions that make up the stable core of
globular proteins; extremes of pH alter the net charge
on the protein, causing electrostatic repulsion and the
disruption of some hydrogen bonding. The denatured
states obtained with these various treatments need not
be equivalent.
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