The concept of a structural domain is important to our understanding of structure/function relationships in both ribonucleic acids and proteins. The term domain refers to a sequence fragment that can fold by itself into the same 3D structure that exists in the full 3D structure. A RNA domain may contain hundreds of nucleotides. For example, the secondary structure of 16S rRNA of E. coli is divided into three major domains: the 5′ domain contains 563 nucleotides, the middle domain 351 nucleotides, and the 3′ domain 623 nucleotides. The RNA domains fold independently. Furthermore, the small subunit ribosomal proteins interact exclusively with a single 16S rRNA domain.

A protein domain typically contains 40 to 100 amino acids and can often adopt a stable tertiary structure in the absence of other parts of the protein. Protein domains are therefore stucturally independent units that each have the characteristics of a globular protein. The polypeptide chain wanders back and forth within a domain. Different domains are connected by short segments of the polypeptide chain.