Structural domain

Within a protein, a structural domain ("domain") is an element of overall structure that is self-stabilizing and often folds independently of the rest of the protein chain. Many domains are not unique to the protein products of one gene or one gene family but instead appear in a variety of proteins. Domains often are named and singled out because they figure prominently in the biological function of the protein they belong to; for example, the "calcium-binding domain of calmodulin. Because they are self-stabilizing, domains can be "swapped" by genetic engineering between one protein and another to make chimeras. A domain may be composed of one, more than one or not any structural motifs.

An important tool in the determination of domains is structural alignment and sequence alignment.

Examples of protein structural domains

Phosphotyrosine-binding domain (PTB). PTB domains usually bind to phosphorylated tyrosine residues. They are often found in signal transduction proteins. PTB-domain binding specificity is determined by residues to the amino-terminal side of the phosphotyrosine. Examples: the PTB domains of both SHC and IRS-1 bind to a NPXpY sequence. PTB-containing proteins such as SHC and IRS-1 are important for insulin responses of human cells.
Pleckstrin homology domain (PH). PH domains bind phosphoinositides (PIP2 and PIP3) with high affinity. Given the fact that phosphoinositides are sequestered to the cell membrane due to their long lipophilic tail, the PH domain usually causes localization of the protein in question to the cell membrane, which is useful for expediting activation of the protein and continuation of a signaling pathway.
Src homology 2 domain (SH2). SH2 domains are often found in signal transduction proteins. SH2 domains confer binding to phosphorylated tyrosine (pTyr). Named after the phosphotyrosine binding domain of the src viral oncogene, which is itself a tyrosine kinase. See also: SH3 domain.
Cadherin repeats. Cadherins function as Ca²⁺-dependent cell-cell adhesion proteins. Cadherin domains are extracellular regions which mediate cell-to-cell homophilic binding between cadherins on the surface of adjacent cells.
Armadillo repeats. Named after the β-catenin-like Armadillo protein of the fruit fly Drosophila. These domains are about 40 amino acids long and proteins that contain them often have many tandemly repeated domains. β-catenin is a protein involved in linking cadherin cell adhesion proteins to the cytoskeleton. This type of protein domain is important in transducing WNT signals during embryonic development.
Zinc finger DNA binding domain (ZnF_GATA). ZnF_GATA domain-containing proteins are typically transcription factors that usually bind to the DNA sequence [AT]GATA[AG] of promoters.
Death effector domain (DED). DED allows protein-protein binding by homotypic interactions (DED-DED). Caspase proteases trigger apoptosis via proteolytic cascades. Caspase-8 and caspase-9 bind to specific adaptor molecules via DED domains and this leads to autoactivation of caspases.

See also: structural biology

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