A structure-derived snap-trap mechanism of a multispecific serpin from the dysbiotic human oral microbiome.

The Journal of Biological Chemistry
Theodoros GoulasF Xavier Gomis-Rüth

Abstract

Enduring host-microbiome relationships are based on adaptive strategies within a particular ecological niche. Tannerella forsythia is a dysbiotic member of the human oral microbiome that inhabits periodontal pockets and contributes to chronic periodontitis. To counteract endopeptidases from the host or microbial competitors, T. forsythia possesses a serpin-type proteinase inhibitor called miropin. Although serpins from animals, plants, and viruses have been widely studied, those from prokaryotes have received only limited attention. Here we show that miropin uses the serpin-type suicidal mechanism. We found that, similar to a snap trap, the protein transits from a metastable native form to a relaxed triggered or induced form after cleavage of a reactive-site target bond in an exposed reactive-center loop. The prey peptidase becomes covalently attached to the inhibitor, is dragged 75 Å apart, and is irreversibly inhibited. This coincides with a large conformational rearrangement of miropin, which inserts the segment upstream of the cleavage site as an extra β-strand in a central β-sheet. Standard serpins possess a single target bond and inhibit selected endopeptidases of particular specificity and class. In contrast, miropin uni...Continue Reading

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Citations

Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alicja Sochaj-GregorczykJan Potempa
Apr 11, 2018·PeerJ·Jialing BaoZeyang Zhou
Mar 30, 2021·Frontiers in Cellular and Infection Microbiology·Qingsong JiangMingyun Li
Mar 22, 2021·Molecular Biology and Evolution·Matthew A SpenceColin J Jackson
Jul 3, 2021·International Journal of Molecular Sciences·Héla MkaouarMoez Rhimi
Jul 3, 2021·International Journal of Molecular Sciences·Gillian A Kelly-RobinsonS Lorraine Martin

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