Wednesday, October 27, 2010

Protein Splicing : Inteins and Exteins

Protein splicing with inteins(protein introns), exteins(protein exons) was discovered some 20 years ago. Not to mention, this process is efficient and autocatalytic where the intein excises itself from the primary protein product (precursor protein) and then catalyzes the joining of the broken ends forming 2 protein products: 1) The mature protein 2) Intein itself.  So, the protein fragments that are joined together to form the mature protein is called as exteins(Same as RNA exons), and inteins are the protein introns.

                   Fig reference: Elleuche S, Pöggeler S. Applied Microbial Biotechnology,2010

All these inteins have sequence similarity with homing nucleases. Homing nucleases are very interesting class of proteins that cleaves the DNA at a particular recognition site. The recognition site is long enough(12 - 40 bp, as against restriction enzymes that recognize 8 bp or less) to occur in a genome by chance. Usually the proteins encoding homing nucleases occur inside the DNA element that is the recognition site for cleavage by themselves. Thus preventing the cleavage of the DNA sequence that carries them, so they are a class of selfish genes. It is very interesting how these homing nucleases propagate themselves to their non-allelic forms. The allele that has homing nuclease is called as HEG+ and the one not having it is called as HEG-. Usually the HEG+ alleles cleave the HEG- gene thus initiating homologous recombination DNA repair. Once repair is initiated, HEG+ is copied at the HEG- locus thus propagating it.
There are currently 4 structural domains of homing endonucleases:
1)LAGLIDADG: If present alone, needs a homodimer to act against a DNA sequence.
2)GIY-YIG: Acts as a monomer, occurs in the N terminus.
3)His-Cys box: 2 histidines and 3 cysteins, acts as a monomer.
4)H-N-H: 2 pairs of histidines flanking one asparagine.

A list of intein integrated sites are listed here [Link
Intein database is [Here]