Protein structure is classified in a hierarchical manner into primary structure, secondary structure, tertiary structure, and quaternary structure. The tertiary structure refers to the overall three-dimensional fold of the polypeptide chain of the protein. Some fibrous proteins (eg, collagen) adopt a regular repeating three-dimensional structure. In contrast, the tertiary structure of most proteins is much more complex and is formed by packing of the protein’s secondary structural elements into one or more compact globular units (usually called domains ). The tertiary structure provides information on the three-dimensional structure of each of the domains and on how the domains pack together. The complexity and diversity of protein tertiary structure gives rise to the complexity and diversity of protein function. Defining what a protein looks like, by determining its tertiary structure, is a significant step in understanding the biological function of that protein.
The tertiary structure of a protein is difficult to predict (see Protein Structure Prediction) but can be determined experimentally by protein X-ray crystallography, nuclear magnetic resonance (NMR) or cryoelectron microscopy. The stable folded tertiary structure of a protein conforms to certain rules of protein structure. For example, the side chains of most globular proteins are distributed in a nonrandom manner. Most hydrophobic residues are located in the inner core of the structure, and charged side chains are generally found on the surface. In addition, more than 90% of amino acid residues in a protein usually adopt backbone conformations that correspond to the a-helices, b-sheets, or turns type of secondary structure. These and other rules are used to assess the quality of experimentally determined structures and can be used to both assist and validate protein structure prediction.
