Structural domain
From Wikipedia, the free encyclopedia
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. Most domains can be classified into "folds". Many domains are not unique to the proteins produced by one gene or one gene family but instead appear in a variety of proteins. Domains often are named and singled out because they play an important role 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 chimera proteins. A domain may be composed of none, one, or many structural motifs.
Important tools in determining domains are structural alignment and sequence alignment.
Designability is the number of amino acid sequences that encode a fold. Folds with higher designability may be more resistant to disease and mutation. Many hereditary disease-associated proteins have folds estimated to be of low designability. [1]
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[edit] Examples
- Arginine Finger
- Armadillo repeats. Named after the β-catenin-like Armadillo protein of the fruit fly Drosophila.
- Basic Leucine zipper domain (bZIP domain) is found in many DNA-binding eukaryotic proteins. One part of the domain contains a region that mediates sequence-specific DNA-binding properties and the Leucine zipper that is required for the dimerization of two DNA-binding regions. The DNA-binding region comprises a number of basic aminoacids such as arginine and lysine
- 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.
- Death effector domain (DED) allows protein-protein binding by homotypic interactions (DED-DED). Caspase proteases trigger apoptosis via proteolytic cascades. Pro-Caspase-8 and pro-caspase-9 bind to specific adaptor molecules via DED domains and this leads to autoactivation of caspases.
- 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 with high affinity. Specificity for PtdIns(3)P, PtdIns(4)P, PtdIns(3,4)P2, PtdIns(4,5)P2, and PtdIns(3,4,5)P3 have all been observed. Given the fact that phosphoinositides are sequestered to various cell membranes (due to their long lipophilic tail) the PH domains usually cause localization of the protein in question to one or another cell membrane, which is useful for expediting activation of the protein and continuation of a signaling pathway. A large number of PH domains have poor affinity for phosphoinositides and are hypothesized to function as protein binding domains.
- 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.
- 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.
[edit] See also
[edit] External links
- The Protein Families (Pfam) database clan browser provides easy access to information about protein structural domains. A clan contains two or more Pfam families that have arisen from a single evolutionary origin.
[edit] Domain databases
- NCBI Conserved Domain Database
- Pfam Domain Database
- SMART Domain Database
- Pawson Lab - Protein interaction domains
- Nash Lab - Protein interaction domains in Signal Transduction
- Definition and assignment of structural domains in proteins.
| Protein tertiary structure | ||
|---|---|---|
| General: | Structural domain | Protein folding | |
| All-α folds: | Helix bundle | Globin fold | Homeodomain fold | Alpha solenoid | |
| All-β folds: | Immunoglobulin fold | Beta barrel | Beta-propeller domain | |
| α/β folds: | TIM barrel | Leucine-rich repeat | Flavodoxin fold | Thioredoxin fold | Trefoil knot fold | |
| α+β folds: | Ferredoxin fold | Ribonuclease A | SH2-like fold | |
| Irregular folds: | Conotoxin | |
| ←Secondary structure | Structure determination methods | Quaternary structure→ |
| Proteins |
|---|
|
Protein biosynthesis | Posttranslational modification | Protein folding | Protein structure | Protein structural domains | Protein targeting | Proteasome | List of proteins | Membrane protein | Globular protein | Fibrous protein | List of types of proteins | Proteome | Protein methods |
