Protein Families - Protein Domains and Motifs

Protein Domains and Motifs

The concept of protein family was conceived at a time when very few protein structures or sequences were known; at that time, primarily small, single-domain proteins such as myoglobin, hemoglobin, and cytochrome c. Since that time, it was found that many proteins comprise multiple independent structural and functional units or domains. Due to evolutionary shuffling, different domains in a protein have evolved independently. This has led, in recent years, to a focus on families of protein domains. A number of online resources are devoted to identifying and cataloging such domains (see list of links at the end of this article).

Regions of each protein have differing functional constraints (features critical to the structure and function of the protein). For example, the active site of an enzyme requires certain amino acid residues to be precisely oriented in three dimensions. On the other hand, a protein–protein binding interface may consist of a large surface with constraints on the hydrophobicity or polarity of the amino acid residues. Functionally constrained regions of proteins evolve more slowly than unconstrained regions such as surface loops, giving rise to discernible blocks of conserved sequence when the sequences of a protein family are compared (see multiple sequence alignment). These blocks are most commonly referred to as motifs, although many other terms are used (blocks, signatures, fingerprints, etc.). Again, a large number of online resources are devoted to identifying and cataloging protein motifs (see list at end of article).