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. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl A peptide bond is a Chemical bond formed between two Molecules when the Carboxyl group of one molecule reacts with the Inteins have also been called "protein introns". Introns, derived from the term "intragenic regions" and also called intervening sequence (IVS are DNA regions in a Gene that are not translated into [1]
Most reported inteins also contain an endonuclease domain that plays a role in intein propagation. Endonucleases are Enzymes that cleave the Phosphodiester bond within a Polynucleotide chain in contrast to Exonucleases which cleave Phosphodiester In fact, many genes have unrelated intein-coding segments inserted at different positions. History See also History of genetics The existence of genes was first suggested by Gregor Mendel (1822-1884 who in the 1860s studied inheritance 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 parasitic. Parasitism is a type of symbiotic relationship between Organisms of different Species. The difference is that "selfish genes" are "selfish" only insofar as to compete with other genes or alleles, but still fulfill a beneficial function for the organism as a whole, whereas "parasitic genes" are functionless. An allele (ˈæliːl (UK /əˈliːl/ (US (from the Greek αλληλος allelos, meaning each other) is one member of a pair or series of different forms
Intein-mediated protein splicing occurs after mRNA has been translated into a protein. Protein splicing is an intramolecular reaction of a particular Protein in which an internal protein segment (called an Intein) is removed from a precursor protein Messenger ribonucleic acid ( mRNA) is a molecule of RNA encoding a chemical "blueprint" for a Protein product 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. Year 1987 ( MCMLXXXVII) was a Common year starting on Thursday (link displays 1987 Gregorian calendar) Since then, inteins have been found in all three domains of life (eukaryotes, bacteria, and archaea). Knowledge regarding the evolutionary situation of inteins and related elements is reviewed in Gogarten & Hilario (2006). eVolution is the third Album by eLDee, it was due to be released in 2008 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. Native chemical ligation is the most widely used form of Chemical ligation, a technique for constructing a large Polypeptide from two or more unprotected peptides
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Inteins in biotechnology
Inteins are very efficient at protein splicing and they have accordingly found an important role in biotechnology. Biotechnology is Technology based on Biology, especially when used in Agriculture, Food science, and Medicine. 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,[2] and the selective labeling of protein segments, which is useful for NMR studies of large proteins. Protein nuclear magnetic resonance spectroscopy (usually abbreviated protein NMR) is a field of Structural biology in which NMR spectroscopy is used [3]
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. Drug development or preclinical development is defined in many pharmaceutical companies as the process of taking a new chemical lead through the stages necessary to allow it
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). Allotopic expression (AE refers to expression from the nuclear Genome of Genes that normally are expressed only from the Mitochondrial genome Gene therapy is the insertion of Genes into an individual's cells and tissues to treat a Disease, and Hereditary diseases in which a The hydrophobicity of these proteins is an obstacle to their import into mitochondria. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. 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. A mutant is an individual organism or new genetic character arising or resulting from an instance of Mutation, which is a base-pair sequence change within the DNA
Intein naming conventions
The first part of an intein name is based on the 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 gene domain in addition to the splicing domains. The Selfish gene theory postulates that Natural selection will increase the frequency of those genes whose phenotypic effects ensure their successful replication. 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 double-stranded break repair (DSBR) system, which then repairs the break, thus copying the intein into a previously intein free site. Homologous chromosomes are Chromosomes in a Biological cell that pair ( synapse) during Meiosis, or alternatively non-identical chromosomes that DNA repair refers to a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its Genome. 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. Cyanobacteria, also known as blue-green algae, blue-green bacteria or Cyanophyta, is a phylum of Bacteria that obtain their energy DnaE is the catalytic subunit of DNA polymerase III, as well as the name of the Gene which encodes that Protein. 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 doi:10. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. 1016/S0167-7799(00)01476-1 (HTML abstract)
- Gogarten, J. Peter & Hilario, Elena (2006): Inteins, introns, and homing endonucleases: recent revelations about the life cycle of parasitic genetic elements. BMC Evolutionary Biology 6: 94 doi:10.1186/1471-2148-6-94 PDF fulltext
- ^ Anraku Y, Mizutani R, Satow Y (2005). BioMed Central ( BMC) is a UK -based for-profit scientific publisher specialising in Open access publication A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. "Protein splicing: its discovery and structural insight into novel chemical mechanisms". IUBMB Life 57 (8): 563–74. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16118114.
- ^ Schwarzer D, Cole PA (2005). "Protein semisynthesis and expressed protein ligation: chasing a protein's tail". Curr Opin Chem Biol 9 (6): 561–9. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16226484.
- ^ Muralidharan V, Muir TW (2006). "Protein ligation: an enabling technology for the biophysical analysis of proteins". Nat. Methods 3 (6): 429–38. doi:. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16721376.
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