Proteins are macromolecule polymers, composed of a long chain of amino acid residues. One of the fundamental building blocks of life, proteins are responsible for a substantial number of biological functions, from acting as enzymes to speed up chemical reactions in complex pathways such as metabolism, to providing basic structural support and composition of the cell.
However, in order to perform these functions properly, proteins require a specific three-dimensional conformation tailored to the purpose for which they were synthesized. While each protein has its own conformation, when analyzing proteins at a molecular level, we tend to describe them using the four levels of protein structure: primary, secondary, tertiary, and quaternary structure.
Primary structure, simply put, refers to the sequence of amino acids stringed together to form a protein. The structure is held together by peptide bonds between the carboxyl and amino group of each amino acid, which is formed during protein translation. Primary structure is heavily dependent upon the DNA sequence within the gene that codes for that particular protein. After being transcribed into mRNA, each triplet within the sequence forms a codon that codes for one amino acid to be added by the ribosome and tRNA to the synthesizing protein. Because the amino acid sequence generated is unique to each protein, and helps determine overall structure and function, any DNA mutation or error in transcription can have serious consequences if it sufficiently alters which amino acid is added to the chain, and can even result in a deactivated, or defunct protein.
Primary structure with peptide bond/linkage
As the chain lengthens, hydrogen bonds can form between the amino acids, which can cause the chain to coil or align in specific ways. This pattern of coiling formed by these bonds is called the secondary structure of the protein. There are two major patterns in which the secondary structure can appear, the (alpha) helix and the (beta) pleated sheet.
The alpha helix looks like a right-handed coil, with the R-groups extending outward from the peptide backbone. The coiling of the helix results from hydrogen bonds that result between the partially positive ( +) hydrogen within a N-H in one amino acid, and the partially negative oxygen ( -) in the C=O bond of another amino acid. You may remember from high school or college chemistry that the charges on these atoms is formed by differences in electronegativity between their bonded neighbors. The helix is stabilized by repeated hydrogen bonding over a segment of the protein.
Alpha Helix (Very) Rough Sketch
The beta pleated sheet, as the name may suggest, looks like a “sheet” of amino acid chains, and is formed when a two or more segment of polypeptide chains are aligned parallel to one another. Hydrogen bonds formed at the ends of the chain stabilize the sheet, similar to the alpha helix.
Beta Pleated Sheet (Very) Rough Sketch
One major point of confusion students have when learning about protein structure is the differentiating between secondary and tertiary structure. A large part of this is due to the fact that the textbook definition of tertiary structure, the bending and folding of the polypeptide chain, sounds very similar to the specific pattern of coiling described within secondary structure. However, once outlined, there are differences between the descriptions that can make it clear why they are considered two different levels of protein structure.
The first major difference between secondary and tertiary structure is the types of bonds involved in the formation of both. While secondary structure is created solely by hydrogen bonding between the N-H and C=O groups on the amino acid chain backbone, the tertiary structure is determined by interactions of amino acid R-groups (also known as side chains), with other R-groups and the environment. These interactions are quite varied in nature, and include things such as disulfide bridges between cysteine side side chains, hydrogen bonding between side chains, ionic attractions to form salt bridges, and aggregation of hydrophobic side chains in water.
Another major difference between secondary and tertiary structure is the possibilities of shapes that can form. Secondary structure is largely limited to the alpha helix and beta pleated sheet formation. On the other hand, tertiary structure can manifest in any number of 3-D configurations. While alpha helices and beta pleated sheets do contribute to portions of these shapes, other large portions of the molecule can form shapes unique to a particular protein. It is important to keep in mind however that these shapes, similar to secondary structure, is derived from and is dependent on the primary structure of the protein. If something, such as the addition of heat were to disrupt the weak interactions within a protein, secondary and tertiary structures would break down, and the protein would be denatured. But, once cooled, it is possible for these bonds to reform and these structures to reoccur, assuming primary structure is not altered.
Many proteins are made from one long polypeptide chain that forms the three levels of structure described above. However, there are some proteins that are formed from multiple polypeptide chains, also known as subunits. How those subunits bind together and interact forms the quaternary structure of a protein. In other words, while all proteins have primary, secondary, and tertiary structure, not all proteins have quaternary structure. When present, the same types of interactions that help form tertiary structure also tend to hold the protein subunits together. Popular examples of proteins with quaternary structure include hemoglobin, which is composed four subunits, and DNA polymerase, which is made up of ten subunits.