Proteins are chains of amino acids that are connected by peptide bonds and folded into a 3-dimensional structure. The side chains of individual amino acid residues determine the interactions among amino acid residues, and ultimately the folding of the protein. Depending on the length and structural complexity, chains of amino acid residues are classified as oligopeptides, polypeptides, or proteins.
An amino acid is a molecule that contains a carboxyl (–COOH) and an amino group (–NH2) attached to the same carbon atom, the ⍺-carbon. The identity of the amino acid is determined by its side chain or side residue, often called the R-group. The simplest amino acid is glycine, where the residue is a single hydrogen atom. Other amino acids carry more complex side chains. The side chain determines the chemical properties of the amino acid. For example, it may attract or repel water (hydrophilic or hydrophobic), carry a negative charge (acidic), or form hydrogen bonds (polar).
Of all known amino acids, only 21 are used to create proteins in eukaryotes (the genetic code encodes only 20 of these). Amino acids are abbreviated using a three letter (e.g., Gly, Val, Pro) or one letter code (e.g., G, V, P). The linear chain of amino acid residues forms the backbone of the protein. The free amino group at one end is called the N-terminus, while the free carboxyl group on the other end constitutes the C-terminus. The chemical properties of the side chains heavily determine the final structure of the protein as they interact with each other and with polar water molecules.
To form a polypeptide, amino acids are linked together by peptide bonds. Peptide bonds are formed between the amino group (–NH2 group) of one amino acid and the carboxyl group (–COOH) of the adjacent amino acid. Proteins are formed by dehydration synthesis. Each one water molecule is formed during linkage of two amino acids. The resulting covalent bond is a peptide bond.
Amino acids have both a basic and an acidic group. They can, therefore, act as a base (hydrogen ion recipient) or as an acid (hydrogen ion donor). The chemical property depends on the pH of the surrounding medium. At low pH (e.g., pH2) both the carboxyl and amino groups are protonated (–NH3, –COOH), so the amino acid acts as a base. At an alkaline pH (e.g., pH13), both the carboxyl and amino groups are deprotonated (–NH2, –COO–) and the amino acid will act as an acid. At a neutral pH (i.e., most physiological environments, ~pH7.4), the amino group is protonated (–NH3) and the carboxyl group is deprotonated (–COO–), giving rise to a zwitterion, a molecule with both a positive and negative charge. These chemical properties at physiological pH are essential to creating hydrogen bonds, which in turn contribute to the formation of more complex protein structures.
Polypeptides are chains of amino acids. Polypeptides with less than 20 amino acids are also referred to as oligopeptides, or simply peptides. A polypeptide chain is referred to as protein when it is folded into a three-dimensional structure, ready to perform its specific cellular function.
Together with carbohydrates, nucleic acids, and lipids, proteins are fundamental building blocks of life. Proteins exhibit enormous diversity in their composition and, hence, function. Among other functions, they provide structure to a cell (e.g., in the form of collagen), allow movement (e.g., actin and myosin in muscles), catalyze reactions (enzymes), bring molecules across the cell membrane, and defend vertebrates against invaders (antibodies).
