BIOL 237 |
| Protein splicing is a post-translational process by which an intervening polypeptide, called an intein, catalyzes its own excision from the flanking polypeptides, called exteins. This excision is concomitant with the ligation of the exteins. The chemical steps of splicing are understood for most inteins, and are initiated by an amide-to-thioester or ester rearrangement of the peptide bond linking the N-terminal extein and intein. However, some inteins lack an N-terminal nucleophile and cannot facilitate this step. The intein that interrupts a putative phage terminase (TerA) in Clostridium thermocellum has a Gln in place of the highly conserved Cys or Ser at its N-terminus. The intein bypasses this first step of splicing and facilitates the direct attack of a Ser hydroxyl at the downstream splice junction on the peptide bond at the N-terminal splice junction. The intein can promote splicing, albeit to a reduced extent, with Ala, Ser, Cys, or Glu in place of the N-terminal Gln. The N-terminal scissile peptide bond is susceptible to hydrolysis if the downstream Ser nucleophile is replaced with Ala by mutagenesis. This activity is reminiscent of certain A-type bacterial intein-like (BIL) domains, and it is interesting the C. thermocellum has evolved to contain as many as 10 A-type BIL domains in addition to the TerA intein. This material is based upon work supported by the National Science Foundation under Grant No. 0320824 and CAREER grant No. 0447647. |
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Frontiers in Chemical Biology
5:00 PM-7:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Biological Chemistry |