A very clear and concise definition of tertiary structure appears in Mark’s Medical Biochemistry, which defines this structural level as “the folding pattern of the secondary structure into a three-dimensional conformation”.
Another way of defining it is based on the linkages that maintain this structural level. The tertiary structure of proteins is usually defined as the spatial conformation of the protein stabilized through several interactions between the R side chains of distant amino acids residues. Distant means that they can be very apart in the sequence, but because of the molecule folding, their lateral chains can interact through their functional groups. These interactions stabilize the spatial conformation of the protein.
Hydrophobic interactions are very often the driven force that allows that lateral chain of distant amino acids becomes next each other. In an aqueous environment, non polar lateral chains of amino acids in a peptide or protein tend to cluster together, as a result of the hydrophobic forces. It allows other kinds of interaction between the “new neighbors” amino acids.
The main interactions that maintain the spatial conformation of the proteins are:
Hydrophobic interactions (already mentioned)
Hydrogen bonds between the R side chain of distant amino acids
Already described. The amino acids with non polar lateral chain that can be attracted among them by hydrophobic forces are Alanine, Valine, Leucine, Isoleucine, Phenylalanine, Tyrosine and Tryptophan
Hydrogen bonds between the side chains (R) of distant amino acids
Hydrogen bonds, as we know, are established between very electronegative atom and Hydrogen bonded to Fluoride, Oxygen or Nitrogen.
These bonds can be established between molecules (like in the former example) or between parts of the same molecule, like occurs in proteins.
The amino acids whose lateral chains can form Hydrogen bonds among them that stabilize the tertiary structure are those that have Oxygen or Nitrogen in their lateral chain:
Serine (hydroxyl group)
Threonine (hydroxyl group)
Tyrosine (hydroxyl group)
Glutamate (carboxyl group)
Glutamine (carbamide group)
Aspartate (carboxyl group)
Asparagine (carbamide group)
Lysine (amine group)
Arginine (amidine group)
Histidine (imidazol group)
(The hydrogen bonds between the lateral chains of amino acids, that stabilize the tertiary structure, should not be confounded with the Hydrogen bonds between elements of the peptide bonds, which are characteristics of the secondary structure)
Charged lateral chains of amino acids can interact with charged lateral chains of other amino acids. Amino acids with charged lateral chain are Glutamate, Aspartate, Lysine, Arginine and Histidine. If the amino acids whose lateral chains are interacting have the same charges, the interaction results in repulsion, so the parts of the peptide chain where the amino acids are located, will separate; if they have different charges, the portions of the peptide chain were they are located will be attracted.
Interaction between aspartate and glutamate (both with negative lateral chain).
Interaction between two of the following: Lysine, Arginine, Histidine (all of them with positively charged lateral chain)
Interaction between glutamate or aspartate (negatively charged lateral chains) with Lysine, Arginine or Histidine (positively charged lateral chains).
As you know, cystein has an R-SH group in it lateral chain
Disulfide bridges are formed when two residues of cysteine interact between them, experimenting an oxidation of the sulfhydril groups. As a result both cysteines become linked, forming a cystine residue.
Disulfide bridges are very strong bonds, that can be formed between different parts of the same peptide chain (intrachain bonds) if the cystein residues that form the disulfide bridge are in the same chain, or they can form interchain bonds, maintaining together different peptide chains, if the cysteine residues that form this linkage are present in different peptide chains.
Disulfide bonds are very frequent in proteins. Insulin has intermolecular and intramolecular disulfide bridges. Immunoglobulin chains are maintained together by disulfide bridges. The following diagram represent an immunoglobulin, whose Heavy and Light chains are maintained together by disulfide bridges (represented in red)
Last but not least: the tertiary structure of a protein is intimately related to its function. Proteins that lost the native tridimensional conformation lost their functions. The main causes of losing a native conformation are denaturalization or a mutation (recall that the primary structure –amino acid sequence -determines the higher structures of the protein).
More information about Tertiary structure of proteins can be found at: