A domain is defined as an independent folding unit because often it may be cloned, expressed and purified separately from other domains of a multi-domain protein, and it will still form the same type of structure and could even show activity (e.g. small molecule ligand binding, interactions with other proteins, etc.) similar to that the domain has within the original protein. A fold
is assigned to each protein domain. While some proteins consist of a single domain, others may contain two or more domains with different folds
. At the sequence level domains that have similar fold may or may not be related to each other functionally and evolutionary, however, a fold can still be used to trace the evolutionary origin of a protein. This also means that similarity of folds cannot always be detected by just comparing their amino acid sequences. More on this can be found in the presentation of CATH domain classification database
In addition to domain conservation, there are also other types of conserved structural elements in proteins, called structural motifs
. These are smaller structural units which may be present within different and not necessarily evolutionary related domains. Examples of such motifs include helix-turn-helix motif, β-hairpins, Greek key motif, etc. These motifs are not considered to be independent folding units, rather, they are usually part of the three-dimensional structure. In a page on domains, fold and motifs
more detailed discussion and examples can be found.