Tertiary Structure Domains, Folds, and Motifs Walter R. P. Novak* Department of Chemistry, Wabash College, Crawfordsville, IN, USA Synopsis Proteins are complex and irregular structures; however, proteins possess regions of regularity at a local level in the form of secondary structure elements such as alpha helices and beta sheets. Secondary structure elements can combine to form structural motifs that are found in a variety of proteins. Many different motifs may be combined to form stably folding protein domains. Protein domains are regions of a protein that can stably fold and possess a certain function. Proteins may be made up of one or many domains. Each protein domain has a fold, which refers to the arrangement of secondary structure elements in that domain. Relatively few distinct folds exist with respect to the number of protein sequences; accordingly, one fold may be utilized by many different proteins to perform a range of functions. Introduction The overall three-dimensional structure of a protein chain, including the positions of amino acid side chains, is referred to as the tertiary structure of the protein. Knowledge of protein tertiary structure is essential to understanding how enzymes function and how to design, inhibit, and activate proteins. As the tertiary structure of the protein is specific to a particular protein sequence, several additional terms describe the architecture of proteins in three-dimensional space, and these terms facilitate the comparison of different proteins on several levels. Protein structures are often composed of independently folding units within the same protein chain, called domains. Every protein domain has a fold, which refers to the arrangement of secondary structure elements in that domain. Protein domains often contain specific arrangements of a few contiguous secondary structure elements. Such units of secondary structure groups that are repeatedly found in a variety of proteins are called motifs or supersecondary structures. Motifs are unable to fold independently and often do not perform a specific function, thus discriminating motifs from protein domains. Levels of Protein Structure Proteins can be described using four levels or structures: the primary structure, or amino acid sequence of the protein; the secondary structure, or the local spatial arrangement of the polypeptide backbone atoms, often organized into regular elements such as alpha helices and beta sheets; the tertiary structure of a protein, or the overall structure of a single polypeptide chain; and the quaternary structure, or the arrangement of multiple polypeptide chains. The tertiary structure describes the position of all backbone atoms as well as side-chain atoms in a given polypeptide chain. Using this definition it is clear then that each different protein sequence necessarily has *Email: novakw@wabash.edu Molecular Life Sciences DOI 10.1007/978-1-4614-6436-5_15-3 # Springer Science+Business Media New York 2014 Page 1 of 5