Chapter 4: The Three Dimensional Structure of Proteins
1. Conformation: The spatial arrangement of atoms in a protein or any part of
a protein. The possible conformations of a protein or protein segment include any
structural state it can achieve without breaking covalent bonds.
2. Native proteins: The biologically active conformation of a macromolecule.
Proteins in any of their functional, folded conformations
3. Intrinsically disordered: For the vast majority of proteins, a particular
structure or small set of structures is critical to function. However, in many cases,
parts of proteins lack discernible structure.
These protein segments are intrinsically disordered. In a few cases, entire
proteins are intrinsically disordered, yet are fully functional.
4. Stability: In the context of protein structure, the term stability can be defined
as the tendency to maintain a native conformation
5. A Protein's Conformation Is Stabilized Largely by Weak Interactions:
The chemical interactions that counteract these effects and stabilize the native
conformation include disulfide (covalent) bonds and the weak (noncovalent)
interactions and forces described in Chapter 2: hydrogen bonds, the hydrophobic
effect, and ionic interactions.
For all proteins of all organisms, weak interactions are especially important in
the folding of polypeptide chains into their secondary and tertiary structures. The
association of multiple polypeptides to form quaternary structures also relies on
these weak interactions.
6. Protein conformation with lowest free energy: In general, the protein
conformation with the lowest free energy (that is, the most stable conformation) is
the one with the maximum number of weak interactions.
7. Hydrophobic group and polar/charged groups: The hydrophobic effect is
clearly important in stabilizing conformation; the interior of a structured protein is
generally a densely packed core of hydrophobic amino acid side chains. It is also
important that any polar or charged groups in the protein interior have suitable
partners for hydrogen bonding or ionic interactions.
8. van der Waals interactions: In the tightly packed atomic environment of a
protein, one more type of weak interaction can have a significant effect: van der
Waals interactions.
Van der Waals interactions are dipole-dipole interactions involving the permanent
electric dipoles in groups such as carbonyls, transient dipoles derived from
,fluctuations of the electron cloud surrounding any atom, and dipoles induced by
interaction of one atom with another that has a permanent or transient dipole.
As atoms approach each other, these dipole-dipole interactions provide an
attractive intermolecular force that operates only over a limited intermolecular
distance. Van der Waals interactions are weak and, individually, contribute little to
overall protein stability. However, in a well-packed protein, or in an interaction
between a protein and another protein or other molecule at a complementary
surface, the number of such interactions can be substantial.
9. Most of the structural patterns outlined:: (1) hydrophobic residues are
largely buried in the protein interior, away from water, and
(2) the number of hydrogen bonds and ionic interactions within the protein is
maximized, thus reducing the number of hydrogen-bonding and ionic groups that
are not paired with a suitable partner.
Proteins within membranes and proteins that are intrinsically disordered or have
intrinsically disordered segments follow different rules. This reflects their particular
function or environment, but weak interactions are still critical structural elements.
10. The Peptide Bond Is Rigid and Planar: C—N bonds, because of their
partial double-bond character, cannot rotate freely.
Rotation is permitted about the N—C±and the C ±—C bonds.
The backbone of a polypeptide chain can thus be pictured as a series of rigid
planes, with consecutive planes sharing a common point of rotation at C±.
The rigid peptide bonds limit the range of conformations possible for a
polypeptide chain.
11. The planar peptide group: Each peptide bond has some double-bond
character due to resonance and cannot rotate.
Although the N atom in a peptide bond is often represented with a partial positive
charge, careful consideration of bond orbitals and quantum mechanics indicates
that the N has a net charge that is neutral or slightly negative.
, .
Three bonds separate sequential ±carbons in a polypeptide chain. The N—C ±and
C±—C bonds can rotate, described by dihedral angles designated Õ and È,
respectively.
The peptide C—N bond is not free to rotate.
12 Peptide conformation is defined by three dihedral angles (also known as
torsion angles): called Õ (phi), È(psi), and É (omega), reflecting rotation about
each of the three repeating bonds in the peptide backbone.
13. Ramachandran plot: The Ramachandran plot is a visual description of the
combinations of Õ and Èdihedral angles that are permitted in a peptide backbone
and those that are not permitted due to steric constraints.
14. Interpreting the Ramachandran plot: Peptide conformations are defined by
the values of Õ and È. Conformations deemed possible are those that involve little
or no steric interference, based on calculations using known van der Waals radii
and dihedral angles.
The areas shaded dark blue represent conformations that involve no steric
overlap if the van der Waals radii of each atom are modeled as a hard sphere and
that are thus fully allowed. Medium blue indicates conformations permitted if
atoms are allowed to approach each other by an additional 0.1 nm, a slight clash.
The lightest blue indicates conformations that are permissible if a very modest
flexibility (a few degrees) is allowed in the É dihedral angle that describes the
peptide bond itself (generally constrained to 180°). The white regions are
conformations that are not allowed.
15. Secondary structure: The local spatial arrangement of the main-chain
atoms in a segment of a polymer (polypeptide or polynucleotide) chain. without
regard to the positioning of its side chains or its relationship to other segments
A regularsecondary structure occurs when each dihedral angle, Õ and È, remains
the same or nearly the same throughout the segment.
There are a few types of secondary structure that are particularly stable and occur
widely in proteins. The most prominent are the ±-helix and ² conformations;
another common type is the ² turn.
16. The ±Helix Is a Common Protein Secondary Structure : A helical
conformation of a polypeptide chain, usually right-handed, with maximal
1. Conformation: The spatial arrangement of atoms in a protein or any part of
a protein. The possible conformations of a protein or protein segment include any
structural state it can achieve without breaking covalent bonds.
2. Native proteins: The biologically active conformation of a macromolecule.
Proteins in any of their functional, folded conformations
3. Intrinsically disordered: For the vast majority of proteins, a particular
structure or small set of structures is critical to function. However, in many cases,
parts of proteins lack discernible structure.
These protein segments are intrinsically disordered. In a few cases, entire
proteins are intrinsically disordered, yet are fully functional.
4. Stability: In the context of protein structure, the term stability can be defined
as the tendency to maintain a native conformation
5. A Protein's Conformation Is Stabilized Largely by Weak Interactions:
The chemical interactions that counteract these effects and stabilize the native
conformation include disulfide (covalent) bonds and the weak (noncovalent)
interactions and forces described in Chapter 2: hydrogen bonds, the hydrophobic
effect, and ionic interactions.
For all proteins of all organisms, weak interactions are especially important in
the folding of polypeptide chains into their secondary and tertiary structures. The
association of multiple polypeptides to form quaternary structures also relies on
these weak interactions.
6. Protein conformation with lowest free energy: In general, the protein
conformation with the lowest free energy (that is, the most stable conformation) is
the one with the maximum number of weak interactions.
7. Hydrophobic group and polar/charged groups: The hydrophobic effect is
clearly important in stabilizing conformation; the interior of a structured protein is
generally a densely packed core of hydrophobic amino acid side chains. It is also
important that any polar or charged groups in the protein interior have suitable
partners for hydrogen bonding or ionic interactions.
8. van der Waals interactions: In the tightly packed atomic environment of a
protein, one more type of weak interaction can have a significant effect: van der
Waals interactions.
Van der Waals interactions are dipole-dipole interactions involving the permanent
electric dipoles in groups such as carbonyls, transient dipoles derived from
,fluctuations of the electron cloud surrounding any atom, and dipoles induced by
interaction of one atom with another that has a permanent or transient dipole.
As atoms approach each other, these dipole-dipole interactions provide an
attractive intermolecular force that operates only over a limited intermolecular
distance. Van der Waals interactions are weak and, individually, contribute little to
overall protein stability. However, in a well-packed protein, or in an interaction
between a protein and another protein or other molecule at a complementary
surface, the number of such interactions can be substantial.
9. Most of the structural patterns outlined:: (1) hydrophobic residues are
largely buried in the protein interior, away from water, and
(2) the number of hydrogen bonds and ionic interactions within the protein is
maximized, thus reducing the number of hydrogen-bonding and ionic groups that
are not paired with a suitable partner.
Proteins within membranes and proteins that are intrinsically disordered or have
intrinsically disordered segments follow different rules. This reflects their particular
function or environment, but weak interactions are still critical structural elements.
10. The Peptide Bond Is Rigid and Planar: C—N bonds, because of their
partial double-bond character, cannot rotate freely.
Rotation is permitted about the N—C±and the C ±—C bonds.
The backbone of a polypeptide chain can thus be pictured as a series of rigid
planes, with consecutive planes sharing a common point of rotation at C±.
The rigid peptide bonds limit the range of conformations possible for a
polypeptide chain.
11. The planar peptide group: Each peptide bond has some double-bond
character due to resonance and cannot rotate.
Although the N atom in a peptide bond is often represented with a partial positive
charge, careful consideration of bond orbitals and quantum mechanics indicates
that the N has a net charge that is neutral or slightly negative.
, .
Three bonds separate sequential ±carbons in a polypeptide chain. The N—C ±and
C±—C bonds can rotate, described by dihedral angles designated Õ and È,
respectively.
The peptide C—N bond is not free to rotate.
12 Peptide conformation is defined by three dihedral angles (also known as
torsion angles): called Õ (phi), È(psi), and É (omega), reflecting rotation about
each of the three repeating bonds in the peptide backbone.
13. Ramachandran plot: The Ramachandran plot is a visual description of the
combinations of Õ and Èdihedral angles that are permitted in a peptide backbone
and those that are not permitted due to steric constraints.
14. Interpreting the Ramachandran plot: Peptide conformations are defined by
the values of Õ and È. Conformations deemed possible are those that involve little
or no steric interference, based on calculations using known van der Waals radii
and dihedral angles.
The areas shaded dark blue represent conformations that involve no steric
overlap if the van der Waals radii of each atom are modeled as a hard sphere and
that are thus fully allowed. Medium blue indicates conformations permitted if
atoms are allowed to approach each other by an additional 0.1 nm, a slight clash.
The lightest blue indicates conformations that are permissible if a very modest
flexibility (a few degrees) is allowed in the É dihedral angle that describes the
peptide bond itself (generally constrained to 180°). The white regions are
conformations that are not allowed.
15. Secondary structure: The local spatial arrangement of the main-chain
atoms in a segment of a polymer (polypeptide or polynucleotide) chain. without
regard to the positioning of its side chains or its relationship to other segments
A regularsecondary structure occurs when each dihedral angle, Õ and È, remains
the same or nearly the same throughout the segment.
There are a few types of secondary structure that are particularly stable and occur
widely in proteins. The most prominent are the ±-helix and ² conformations;
another common type is the ² turn.
16. The ±Helix Is a Common Protein Secondary Structure : A helical
conformation of a polypeptide chain, usually right-handed, with maximal
