Details

Autor(en) / Beteiligte

• Garcia-Ferrer, Irene
• Arêde, Pedro
• Gómez-Blanco, Josué
• Luque, Daniel
• Duquerroy, Stephane
• Castón, José R.
• Goulas, Theodoros
• Gomis-Rüth, F. Xavier

Titel

Structural and functional insights intoEscherichia coliα₂-macroglobulin endopeptidase snap-trap inhibition

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2015-07, Vol.112 (27), p.8290-8295

Ort / Verlag

National Academy of Sciences

Erscheinungsjahr

2015

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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, α₂-macroglobulin (α₂M).Escherichia coliα₂M (ECAM) is a ∼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.”