Protein Structure and Function

Protein Structure and Function

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 linkedtogether. 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. Secondarystructure is the arrangement in space of the atoms in the peptide backbone.The α-helix and β-pleated sheet arrangements are two different types of sec-ondary 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 structure.

Tertiary structure includes the three-dimensional arrangement of all theatoms in the protein, including those in the side chains and in any prostheticgroups (groups of atoms other than amino acids).

A protein can consist of multiple polypeptide chains called subunits. The arrangement of subunits with respect to one another is the quaternary structure. Interaction between subunits is mediated by noncovalent interactions, such as hydrogen bonds, electrostatic attractions, and hydrophobic interactions.

Summary

Proteins are made up of long chains of amino acids. The composition and order of the amino acids are critical to the protein function.

For any native protein, there is one, or at most a few, three-dimensional structures that function correctly.

Protein structure can be classified into primary, secondary, tertiary, and quaternary structure.

Primary structure is the order of the amino acids. Secondary structure is characterized by a repetitive organization of the peptide backbone. Tertiary structure refers to the complete three-dimensional structure of the protein. Quaternary structure describes a protein that has multiple polypeptide chains.