Proteins are long chains of amino acids that fold into stable three-dimensional structures called native conformation. Proteins undergo four levels of hierarchical organization: primary, secondary, tertiary, and quaternary, to form their native conformation. Proteins are synthesized as long chains of amino acids that fold locally into one or more secondary structures, such as alpha-helix, beta-sheets, or beta-turns. The locally folded polypeptide chains come closer, forming the more compact tertiary structures. The tertiary structure of proteins is their most stable conformation and often the functionally active form. However, proteins made of more than one polypeptide chain become active only after assembling their constituent folded polypeptide chains (subunits). Such supramolecular complexes are also called the quaternary structures of proteins.

The Order of Amino Acids Determines the Primary Structure

The linear sequence of amino acids constituting a polypeptide is the primary structure of proteins. Amino acids are held together by covalent peptide bonds formed between an amino (–NH3) group of one amino acid and the carboxyl (–COOH) group of the following amino acid. This repeating series of carbon, oxygen and nitrogen atoms is called the polypeptide backbone. Side chains of amino acids stick out perpendicularly from the backbone.

Hydrogen Bonds among Close Amino Acid Residues Contribute to the Secondary Structure

Secondary structures arise when nearby amino acids allow the amide hydrogen and carbonyl oxygens of the polypeptide backbone to engage in hydrogen bonding. Alpha-helix, beta-sheets, and beta-turns are some common local secondary structures. Alpha-helices are formed when the hydrogen atom of an amino group of one amino acid interacts with the carbonyl oxygen of every fourth amino acid of a polypeptide chain. In contrast, beta-pleated sheets are formed by hydrogen bonding between segments of the polypeptide chain, arranged side by side, or between two separate polypeptide chains.

The Interactions of Distant Side Chains Determine the Tertiary Structure

The tertiary structure is the 3-dimensional arrangement of a polypeptide chain. Tertiary structure is formed when side chain residues of distant amino acid residues come together and interact via multiple weak or non-covalent bonds such as ionic bonds, hydrophobic interactions, and hydrogen bonds. The tertiary structure of polypeptides also contains strong covalent bonds like disulfide bridges that help stabilize the protein.

Multiple Polypeptide Chains Can Form a Single Protein

So far, we have considered proteins created from a single polypeptide chain. Many proteins consist of subunits that are each formed of one polypeptide chain. The composition and interaction of multiple protein subunits are known as the quaternary structure.