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Publication Abstract from PubMed

The survival of commensal bacteria requires them to evade host peptidases. Gram-negative bacteria from the human gut microbiome encode a relative of the human endopeptidase inhibitor, alpha2-macroglobulin (alpha2M). Escherichia coli alpha2M (ECAM) is a approximately 180-kDa multidomain membrane-anchored pan-peptidase inhibitor, which is cleaved by host endopeptidases in an accessible bait region. Structural studies by electron microscopy and crystallography reveal that this cleavage causes major structural rearrangement of more than half the 13-domain structure from a native to a compact induced form. It also exposes a reactive thioester bond, which covalently traps the peptidase. Subsequently, peptidase-laden ECAM is shed from the membrane and may dimerize. Trapped peptidases are still active except against very large substrates, so inhibition potentially prevents damage of large cell envelope components, but not host digestion. Mechanistically, these results document a novel monomeric "snap trap."

Structural and functional insights into Escherichia coli alpha2-macroglobulin endopeptidase snap-trap inhibition.,Garcia-Ferrer I, Arede P, Gomez-Blanco J, Luque D, Duquerroy S, Caston JR, Goulas T, Gomis-Ruth FX Proc Natl Acad Sci U S A. 2015 Jun 22. pii: 201506538. PMID:26100869^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.