In this tutorial, you will learn why protein folding is important to how a protein functions. You will also learn how a protein folds, explained along side the four levels of protein structure.
Protein Folding is Important to Protein Function
Protein folding is the process in which a protein takes on its shape. In many biology courses, it is often said structure=function, and proteins are no exception. For example the protein hemoglobin takes on a specific shape that allows it to carry oxygen through the body, and the protein collagen has a different but still important structure that allows skin to maintain its elasticity. The shape that a protein takes on is vitally important to how it behaves.
Describing Protein Folding through Structure
Levels of Protein Structure
Four levels of protein structure describe proteins. The most basic being primary structure, which describes a chain of amino acids. Secondary Structure describes the formation of two critical configurations: the alpha helix and beta pleated sheet. Tertiary structure more broadly describes how the protein folds – i.e. how secondary structures and unstructured regions of the protein interact. Quaternary Structure describes how multiple protein chains interact with each other.
The primary level of protein structure, although the most basic, is vital to the shape the protein will take on. The primary sequence of a protein can affect all other levels of protein structure. When amino acids in a protein’s sequence are changed, it is possible for the protein to lose or change its shape.
The secondary structure of a protein describes key features of a folded protein: the alpha helix and the beta pleated sheet. Both of these structures contain hydrogen bonds, but differ in where the hydrogen bonds are formed.
An alpha helix is a strand of amino acids arranged in a coil, much like the coil of DNA. Hydrogen bonds are made from the carbonyl oxygen, and the amide group four positions away (not depicted).
Beta sheets are strands of amino acids that are in line with each other, creating a large sheet of connected amino acids. The strands in a beta pleated sheet can have either the same directionality or alternating directionality, creating parallel and antiparallel beta sheets- respectively.
Our discussion of secondary structure has introduced us to the carbonyl and amino groups (that are present in all amino acids) and to the hydrogen bond. In creating even more unique arrangements of amino acids, even more types of interactions are formed. The carbonyl and amine groups on proteins can interact with each other in more complex ways and can also interact with other chemical features that are unique to each amino acid, present in R groups. Interactions such as electrostatic interactions, and disulfide bonds commonly hold a protein structure together.
Electrostatic interactions form between atoms or molecules based on charge. Amino acid side chains, or R groups, have positive charge, like lysine, negative charge, like aspartic acid, or are neutral like glycine. Positively charged amino acids attract negatively charged amino acids. More generally, positive regions on a protein attract negative regions.
Hydrophobic interactions describe the tendency for hydrophobic residues (non-polar) to have less interaction with water than their more hydrophilic (polar, like water) counterparts. Amino acids that do not have a charge, and are otherwise nonpolar tend to “bunch up,” leaving the polar residues more open to interact with water, and other polar substances.
Disulfide bonds are covalent bonds between sulfur atoms, typically found on the amino acid, Cysteine. Also called disulfide linkages, or bridges, they contribute another way to form connections between amino acids in a protein, and contribute to protein folding.
Quaternary structure describes how two strands of amino acids, or two proteins, interact with each other. The same interactions that are responsible for stabilizing a protein’s tertiary structure also help proteins interact in quaternary structure.
What Affects Protein Folding?
With all of the specific interactions that exist within a folded protein, it might make sense that proteins are only stable under certain conditions. A protein can lose shape due to heat, pH, salinity (the amount of salt present), and the presence of other molecules. As discussed before, changes in the primary structure, or mutations can also effect how a protein is folded.