Intein
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2008-06-14T15:06:31Z
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An '''intein''' is a segment of a [[protein]] that is able to excise itself and rejoin the remaining portions (the exteins) with a [[peptide bond]]. Inteins have also been called "protein [[intron]]s".<ref>{{cite journal |author=Anraku Y, Mizutani R, Satow Y |title=Protein splicing: its discovery and structural insight into novel chemical mechanisms |journal=IUBMB Life |volume=57 |issue=8 |pages=563–74 |year=2005 |pmid=16118114 |doi=10.1080/15216540500215499}}</ref>
Most reported inteins also contain an [[endonuclease]] domain that plays a role in intein propagation. In fact, many [[gene]]s have unrelated intein-coding segments inserted at different positions. For these and other reasons, inteins (or more properly, the gene segments coding for inteins) are sometimes called ''[[selfish genetic elements]]'' but
it may be more accurate to call them [[Parasite|parasitic]]. The difference is that "selfish genes" are "selfish" only insofar as to compete with other genes or [[allele]]s, but still fulfill a beneficial function for the [[organism]] as a whole, whereas "parasitic genes" are functionless.
Intein-mediated [[protein splicing]] occurs after [[mRNA]] has been translated into a protein. This precursor protein contains three segments - an N-extein followed by the intein followed by a C-extein.
After splicing has taken place, the result is also called an extein.
The first intein was discovered in [[1987]]. Since then, inteins have been found in all three domains of life (eukaryotes, bacteria, and archaea). Knowledge regarding the [[evolution]]ary situation of inteins and related elements is reviewed in Gogarten & Hilario (2006).
The mechanism for the splicing effect is a naturally occurring analogy to the technique for chemically generating medium-sized proteins called [[native chemical ligation]], which was developed at the same time as inteins were discovered.
== Inteins in biotechnology ==
Inteins are very efficient at protein splicing and they have accordingly found an important role in [[biotechnology]]. There are more than 200 inteins identified to date, sizes range from 100-800 aa. Inteins have been engineered for particular applications such as protein synthesis,<ref>{{cite journal |author=Schwarzer D, Cole PA |title=Protein semisynthesis and expressed protein ligation: chasing a protein's tail |journal=Curr Opin Chem Biol |volume=9 |issue=6 |pages=561–9 |year=2005 |pmid=16226484 |doi=10.1016/j.cbpa.2005.09.018}}</ref> and the selective labeling of protein segments, which is useful for [[Protein NMR|NMR]] studies of large proteins.<ref>{{cite journal |author=Muralidharan V, Muir TW |title=Protein ligation: an enabling technology for the biophysical analysis of proteins |journal=Nat. Methods |volume=3 |issue=6 |pages=429–38 |year=2006 |pmid=16721376 |doi=10.1038/nmeth886}}</ref>
Pharmaceutical inhibition of intein excision may be a useful tool for [[drug development]], the protein that contains the intein will not carry out its normal function if the intein does not excise since its structure will be disrupted.
It has been suggested that inteins could prove useful for achieving [[allotopic expression]] of certain highly hydrophobic proteins normally encoded by the mitochondrial genome, for example in [[gene therapy]] (de Grey 2000). The hydrophobicity of these proteins is an obstacle to their import into [[mitochondria]]. Therefore, the insertion of a non-hydrophobic intein may allow this import to proceed. Excision of the intein after import would then restore the protein to [[wild-type]].
== Intein naming conventions ==
The first part of an intein name is based on the [[Binomial nomenclature|scientific name]] of the [[organism]] in which it is found, and the second part is based on the name of the corresponding gene or extein. For example, the intein found in ''[[Thermoplasma acidophilum]]'' and associated with 'Vacuolar ATPase subunit A' (VMA) is called 'Tac VMA'.
Normally, as in this example, just three letters suffice to specify the organism, but there are variations. For example, additional letters may be added to indicate a strain.
If more than one intein is encoded in the corresponding gene, the inteins are given a numerical suffix starting from 5' to 3' or in order of their identification. For example, "Msm dnaB-1".
The segment of the gene that encodes the intein is usually given the same name as the intein, but to avoid confusion, the name of the intein proper is usually capitalized (e.g. Pfu RIR1-1), whereas the name of the corresponding gene segment is italicized.
== Full and mini inteins ==
Inteins can contain a [[homing endonuclease genes|homing endonuclease gene]] domain in addition to the splicing domains. This domain is responsible for the spread of the intein by cleaving DNA at an intein free allele on the [[homologous chromosome]], triggering the [[DNA repair#Double strand breaks|DNA double-stranded break repair]] (DSBR) system, which then repairs the break, thus copying the intein into a previously intein free site. The HEG domain is not necessary for intein splicing, and so it can be lost, forming a minimal, or mini intein. Several studies have demonstrated the modular nature of inteins by adding or removing HEG domains and determining the activity of the new construct.
== Split inteins ==
Sometimes, the intein of the precursor protein comes from two genes. In this case, the intein is said to be a split intein. For example, in [[Cyanobacteria]], [[DnaE]], the catalytic subunit alpha of DNA polymerase III, is encoded by two separate genes,
dnaE-n and dnaE-c. The dnaE-n product consists of an N-extein sequence followed by a 123-aa (amino acid) intein sequence, whereas the dnaE-c product consists of a 36-aa intein sequence followed by a C-extein sequence.
== References ==
* '''de Grey''', Aubrey D. N. J. (2000): Mitochondrial gene therapy: an arena for the biomedical use of inteins. ''Trends in Biotechnology'' '''18'''(9): 394-399 <small>{{DOI|10.1016/S0167-7799(00)01476-1}}</small> (HTML abstract)
* '''Gogarten''', J. Peter & '''Hilario''', Elena (2006): Inteins, introns, and homing endonucleases: recent revelations about the life cycle of parasitic genetic elements. ''[[BioMed Central|BMC Evolutionary Biology]]'' '''6''': 94<!-- BMC papers have article instead of page numbers --> <small>{{DOI|10.1186/1471-2148-6-94}}</small> [http://www.biomedcentral.com/content/pdf/1471-2148-6-94.pdf PDF fulltext]
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==External links==
*[http://www.neb.com/neb/inteins.html The Intein Database]
*[http://bioinformatics.weizmann.ac.il/~pietro/inteins/ Shmuel Pietrokovski's Intein database]
[[Category:Proteins]]
[[Category:Molecular genetics]]
[[Category:Protein biosynthesis]]
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