Biochemistry

Forming New Ties Directly

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Science  29 Sep 2000:
Vol. 289, Issue 5488, pp. 2243
DOI: 10.1126/science.289.5488.2243b

The process through which a gene is transformed into a protein is neither simple nor straightforward. Segments of DNA can be rearranged, as in V(D)J recombination, and segments of RNA transcripts can be spliced to remove introns and to join exons. Proteins, too, can be modified, for instance, to cut away a membrane-targeting signal sequence or to snip out shorter pieces for use as neuropeptide transmitters.

Southworth et al. have studied the mechanisms (summarized by Noren et al.) by which protein segments (inteins) can be removed and the remaining pieces (exteins) spliced together. The canonical pathway relies on the reactivity of polar, nucleophilic side chains at the N-termini of both the intein and the downstream extein. They now demonstrate the existence of an alternative pathway in which an internal cysteine attacks directly an upstream peptide bond to form a branched intermediate, which then collapses through intramolecular cyclization and an S → N shift into the linear product and the disposable intein. — GJC

EMBO J.19, 5019 (2000); Angew Chem. Int. Ed.39, 450 (2000).

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