General Index
Tertiary Structure of Proteins
Definition
The Tertiary Structure of a protein is the spatial arrangement of all its atoms. Of all the concepts concerning protein
structure, the tertiary structure is the closest to which is called Absolute configuration in low molecular weight compounds. That is,
the tertiary structure is defined when we know the spatial coordinates X, Y and Z of all its atoms.
The concept of tertiary structure arises when we realize that many proteins, being linear polymers, nevertheless behave as
a compact, globular structure (this can be seen by hydrodynamic measurements, such as intrinsic vistosity or diffussion coefficient).
Let's consider the case of Myoglobin:
Myoglobin is a protein of 153 aminoacids long, with a secondary structure mainly in a-helix:
Forces maintaining tertiary structure
The tertiary structure of a protein is maintained mainly by weak interactions, although covalent bonds may also be
important, namely the disulfide -S-S- established between side chains of cysteine.
The Hydrophobic Effect
Among weak interactions, perhaps the most important, at least in globular proteins, are those determined by the Hydrophobic
Effect.
In a water environment, the hydrophobic residues of a protein tend to be excluded from water, and then we find them mainly in the
interior of the molecule, water being in its turn excluded from it. To illustrate this effect, let's see the molecule of the enzyme Triose
phosphate isomerase:
If we select the hydrophobic residues and we represent them at their van der Waals radius:
Thus, the structure of a protein can be compared to a Micelle. The London-Van der Waals interactions that arise in the
interior of the protein are a basic force in maintaining the tridimensional structure of the protein.
Hydrogen bonds
Hydrogen bonds are not only important in maintaining secondary structure, but also tertiary structure. We can appreciate
that in the same protein:
Disulfide bridges
Some covalent bonds are important in maintaining tertiary structure, namely Disulfide bridges:
We have in this image two consecutive tracts in a-helix, linked by a disulfide bond
established between the side chain of two cysteines:
Other example of disulfide bridge:
We have two tracts withour secondary structure linked by a disulfide:
Structural Domains
Tertiary structure often appears concentrated in the so-called Domains.
The enzyme Papain is a Thiol Proteinase, that is, a proteolytic enzyme whose active center presents a -SH group.
Its structure is:
We can appreciate two "coils" separated by a zone without any secondary structure:
has a different secondary structure (two antiparallel beta-sheets and two alpha-helices).
Sometimes the domains correspond to different functions in the same protein (for example, catalytic and regulatory regions) and
also correspond to discontinuities in genes (exons).
Papain has two different domains. In other proteins, different domains present a similar structure. This is the case of
Elastase, other proteolytic enzyme:
Both domains have a similar structure:
in both domains we see a b-sheet.
We'll see later that this domain structure is conspicuous in the case of
Immunoglobulins.