Describe the nature, structure, and function of domains in proteinsDomains"Within a single subunit [polypeptide chain], contiguous parts of the polypeptide chain frequently fold into units compact and local semi-independent structures called domains" - Richardson, 1981In the hierarchical organization of proteins, domains are found at the highest level of tertiary structure. Since the term was first used by Wetlaufer (1973), a number of definitions exist reflecting the authors' bias, but all definitions agree that domains are independently folded compact units. Domains are frequently encoded by exons and therefore have specific functionalities. Among the many descriptions of protein domains, the two most striking and simplest are "protein evolutionary units" and "protein base currency". Domains can be considered as connected units, which are to varying degrees independent in terms of structure, function and folding behavior. Each domain can be described by its fold. While some proteins are made up of a single domain, others are made up of several or many. A number of globular protein chains are made up of two or three domains appearing as "lobes". In other cases, the domains may be very different in nature – for example, some proteins located in cell membranes have an intracellular or extracellular globular domain distinct from the one that spans the membrane. Protein domains are found in large polypeptides (proteins that have more than 200 residues). These proteins have at least two globular clusters which in turn have domains composed of 100 to 200 amino acids. Thus, many domains are structurally independent units that exhibit characteristics of small globular proteins. If we look at the detailed structures of many transmembrane proteins, we see that they often have three different domains, two hydrophilic and one hydrophobic. (fig 1&2) A hydrophilic domain (made up of hydrophilic amino acids) at the N-terminus appears in the extracellular medium, a hydrophobic domain in the middle of the amino acid chain, often only 20 to 30 amino acids long , is threaded through the plasma membrane and a hydrophilic domain The C-terminal domain protrudes into the cytoplasm. The transmembrane domain, because it is made of amino acids having hydrophobic side chains, exists comfortably within the hydrophobic inner layers of the plasma membrane. Because these transmembrane domains anchor many proteins in the lipid bilayer, these proteins are not free floating and cannot be biochemically isolated and purified without first dissolving the lipid bilayer with detergents. (Indeed, much of the washing we do in our lives is necessitated by the need to solubilize proteins embedded in lipid membranes using detergents.!)