Activating En Passant

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Science  23 Mar 2007:
Vol. 315, Issue 5819, pp. 1638
DOI: 10.1126/science.315.5819.1638b

Autotransporters are a family of bacterial virulence proteins that are first translocated across the inner membrane and then inserted into the outer membrane. The smaller C-terminal domain adopts a β barrel structure that spans the outer membrane and serves as a transitway for the larger N-terminal “passenger” domain, which is transported through the barrel; some passenger domains are released into the extracellular space by proteolysis.

In an extensive series of genetic and biochemical experiments, Dautin et al. show that the passenger domain of Escherichia coli autotransporter EspP is cleaved in an unusual fashion: not by a periplasmic or outer membrane protease, but by itself. Enzymatic hydrolysis of a peptide bond is customarily initiated by an activated nucleophile. Like the classical serine protease catalytic triad, where the carboxylate of an aspartate residue pulls on the hydroxyl proton of the active-site serine (via an intermediary histidine), EspP also uses an aspartate, which happens to reside on the inner surface of the β barrel and is located roughly halfway across the thickness of the outer membrane. This carboxylate pulls on the amide proton of an asparagine residue in the transiting passenger domain; this activates the amide nitrogen for attack on and cleavage of the peptide backbone, yielding a succinimide that could be resolved as a mixture of asparagine and isoasparagine. This asparagine-aspartate self-cleaving mechanism appears to be utilized by other autotransporters as well as by eukaryotic viruses during capsid maturation. — GJC

EMBO J. 26, 10.1038/sj.emboj.7601638 (2007).

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