Amino Acids and Protein Function

Proteins are the workhorses of cells, responsible for nearly every task that goes on inside and outside a cell. They bind and transport molecules, carry chemical signals across the plasma membrane, and activate intracellular processes.


To do their jobs, proteins must have specific shapes. These shapes are determined by the secondary and tertiary levels of protein structure.

Amino Acids

Amino acids are the building blocks of proteins, and their structure determines much of protein function. A protein consists of a sequence of linear chains of amino acid residues that are linked by amide bonds to form a three-dimensional fold. Different amino acids have different properties, which vary according to their shape and polarity, and the presence of other groups (e.g. carboxyl or hydroxyl) on the side chain. There are 21 standard amino acids, which may be arranged in proteins to have a wide range of functional characteristics.

Amino acid side chains are also able to interact with other residues within the protein, and can influence its stability and specificity. Five of the amino acids (phenylalanine, methionine, isoleucine, leucine, and valine) are hydrophobic, and a pattern of folding that leaves these residues buried within a protein interior or exposed to lipids along transmembrane segments is thermodynamically favored. Other nonstandard amino acids such as serine (Ser, S), threonine (Thr, T), asparagine (Asn, N), and glutamine (Gln, Q) are polar and uncharged, and readily hydrogen bond with water. Serine is further distinguished from the other polar amino acids by having two chiral centers, one L (2S) at its a-carbon and the other R (3R) at the b-carbon.

Amino acids enter the body mainly from dietary protein, and are also generated by the breakdown of tissue proteins. They are used in protein synthesis, regulated by enzymes, and excreted in the urine.

Secondary Structure

The primary structure of a protein is determined by the amino acid sequence and determines its unique characteristics and overall chemical properties. The secondary structure, on the other hand, determines its specific three-dimensional shape, which is necessary for its function.

Two of the most common secondary structures are alpha (helix) and beta (pleated sheet). The helices are tight, spiral-like structures and the sheets are flat and often form pleated structures. Both of these are held together by hydrogen bonds between adjacent amino acids chains. In the helix, the C-O of one chain forms a hydrogen bond with the H-N of an adjacent chain; in the beta sheet, the C-C bonds between amino acid chains form hydrogen bonds with each other.

Hydrogen bonding causes the polypeptide chain to helix or fold and these structures are stabilised by nonlocal interactions, including electrostatic forces, disulfide linkages, van der Waals forces, and polar and apolar interaction sites. These interactions lead to a final, functional three-dimensional spatial conformation, termed the tertiary structure of the protein.

In general, the helix and beta sheet structural elements spontaneously form as an intermediate before the proteins fold into their tertiary structures. Other secondary structural elements, such as sharp turns, Omega loops, and random coil are also seen in some proteins. Protein secondary structures are typically assigned by a minimum length requirement for the helix and sheet conformations and a maximum residue size for the turns and loops.

Tertiary Structure

The tertiary structure of proteins is the overall shape that a protein assumes. This is the result of a variety of interactions between different R groups on adjacent amino acids in the polypeptide chain. These interactions can involve ionic, hydrogen, and dipole-dipole bonds; disulfide bridges; and hydrophobic and hydrophilic interactions. This level of protein structure is stabilised by nonlocal interactions and a variety of mechanisms, including the formation of a hydrophobic core.

The final step in protein folding is the creation of a unique three-dimensional molecular shape. Proteins are usually divided into globular and fibrous proteins, which differ in their three-dimensional shapes. The structures of globular proteins are more spherical than the elongated rope-like structures of fibrous proteins. The tertiary structure of a protein is important for its function. For example, enzymes have active sites that are located in deep pockets formed by three-dimensional protein folding. Antibodies are also shaped by a complex tertiary structure that allows them to bind specific antigens. And hemoglobin, the protein that carries oxygen in the blood, has a complex tertiary structure to allow it to bind and release oxygen.

The primary structure of a protein is its linear sequence of amino acid residues that are encoded by its gene (DNA). The secondary structure of a protein is the local folded shape of a polypeptide chain, such as an alpha helix or beta pleated sheet. The tertiary structure of proteins results from the unique interactions between the amino acid side chains of adjacent polypeptide chains to form a three-dimensional shape.

Post-Translational Modifications

Proteins can be modified by a variety of chemical processes that occur either before or after their synthesis. These changes alter their properties and thus influence their biological functions. The most common post-translational modifications (PTMs) are the addition of small modifying groups to amino acids in proteins such as phosphorylation, glycosylation, palmitoylation and ubiquitinylation.

PTMs can significantly affect the three-dimensional structure, electrophilicity and interactions of proteins. Reversible protein phosphorylation on serine, threonine or tyrosine residues is one of the most important and well-studied PTMs in prokaryotes and eukaryotes. The phosphate group can act as a molecular switch that turns on or off the activity of a protein. Phosphorylation is typically mediated by enzymes called kinases and dephosphorylation is catalyzed by phosphatases.

Glycosylation is a major protein modification that affects a wide range of functional properties including protein folding, distribution and stability. It involves the addition of sugar molecules to a protein and can be categorized into different groups based on the type of sugar-peptide bond involved, namely N-linked, O-linked or C-linked glycosylation. Methylation is another common PTM that is characterized by the addition of one-carbon methyl groups to protein side chains. It can be induced by S-adenosyl methionine (SAM) and is mediated by methyltransferases. Other protein modifications such as prenylation, myristoylation and palmitoylation are also important modifying agents with diverse effects.