Biologically active proteins are polymers consisting of amino acids linked by covalent peptide bonds. Many different conformations (three-dimensional structures) are possible for a molecule as large as a protein.
Of these many structures, one or (at most) a few have biological activity; these are called the native conformations. Many proteins have no obvious regular repeating structure. As a consequence, these proteins are frequently described as having large segments of “random structure” (also referred to as random coil).
The term random is really a misnomer, because the same nonrepeating structure is found in the native conformation of all molecules of a given protein, and this conformation is needed for its proper function.
Because proteins are complex, they are defined in terms of four levels of structure.
What are the levels of protein structure?
Primary structure is the order in which the amino acids are covalently linked together. The peptide Leu-Gly-Thr-Val-Arg- Asp-His (recall that the N-terminal amino acid is listed first) has a different primary structure from the peptide Val-His-Asp-Leu- Gly-Arg-Thr, even though both have the same number and kinds of amino acids.
Note that the order of amino acids can be written on one line. The primary structure is the one-dimensional first step in specifying the three-dimensional structure of a protein. Some biochemists define primary structure to include all covalent interactions, including the disulfide bonds that can be formed by cysteines; however, we shall consider the disulfide bonds to be part of the tertiary structure, which will be considered later.
Two three-dimensional aspects of a single polypeptide chain, called the secondary and tertiary structure, can be considered separately. Secondary structure is the arrangement in space of the atoms in the peptide backbone.
The -helix and ‑-pleated sheet arrangements are two different types of secondary structure. Secondary structures have repetitive interactions resulting from hydrogen bonding between the amide N-H and the carbonyl groups of the peptide backbone.
The conformations of the side chains of the amino acids are not part of the secondary structure. In many proteins, the folding of parts of the chain can occur independently of the folding of other parts. Such independently folded portions of proteins are referred to as domains or super-secondary structures.
Native conformations – three-dimensional shapes of proteins with biological activity
Primary structure – the order in which the amino acids in a protein are linked by peptide bonds
Secondary structure – the arrangement in space of the backbone atoms in a polypeptide chain
Domains (super-secondary structure) – specific clusters of secondary structural motifs in proteins
Tertiary structure – the arrangement in space of all the atoms in a protein
Prosthetic groups – portions of proteins that do not consist of amino acids
Subunits – the individual parts of a larger molecule (e.g., the individual polypeptide chains that make up a complete protein)
Quaternary structure – the interaction of several polypeptide chains in a multisubunit protein