A proposed mechanism for the self-splicing of proteins.
Intervening protein sequences, called inteins, are intronlike elements that are removed posttranslationally, apparently by self-splicing. The conserved and essential residues of precursor proteins consist of an asparagine as the last residue of the intein and a hydroxyl- or thiol-containing residue immediately following both splice junctions. Evidence for a branched intermediate has been reported [Xu, M.-Q., Southworth, M., Mersha, F., Hornstra, L. & Perler, F. (1993) Cell 75, 1371-1377]; however, the chemical nature of the branched structure is unclear. I propose a mechanism that includes the formation of a branched structure, provides an explanation for the reversal of branch formation observed at high pH, and accounts for each of the essential amino acids. The branched structure is formed by nucleophilic attack of the asparagine side chain on the N-terminal splice junction. The nature of this branched structure is a distinguishing feature of the model and can be experimentally tested.
Clarke
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Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
D001216:Asparagine; D002384:Catalysis; D004952:Esters; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007094:Imides; D008962:Models, Theoretical; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry*
D004952:Esters; D007094:Imides; D011506:Proteins; D001216:Asparagine