4ZIU

Crystal structure of native alpha-2-macroglobulin from Escherichia coli spanning the residues from domain MG7 to the C-terminus.

Summary for 4ZIU

• Entry DOI: 10.2210/pdb4ziu/pdb
• Related: 4ZIQ
• Descriptor: Uncharacterized lipoprotein YfhM, NICKEL (II) ION, GLYCEROL, ... (4 entities in total)
• Functional Keywords: bacterial pan-proteinase inhibitor, membrane protein and inhibitor complex, membrane protein-inhibitor complex, membrane protein/inhibitor
• Biological source: Escherichia coli K-12
• Total number of polymer chains: 1
• Total formula weight: 70196.38

Authors

Garcia-Ferrer, I.,Arede, P.,Gomez-Blanco, J.,Luque, D.,Duquerroy, S.,Caston, J.R.,Goulas, T.,Gomis-Ruth, X.F. (deposition date: 2015-04-28, release date: 2015-06-10, Last modification date: 2024-05-01)

Primary citation

Garcia-Ferrer, I.,Arede, P.,Gomez-Blanco, J.,Luque, D.,Duquerroy, S.,Caston, J.R.,Goulas, T.,Gomis-Ruth, F.X.
Structural and functional insights into Escherichia coli alpha 2-macroglobulin endopeptidase snap-trap inhibition.
Proc.Natl.Acad.Sci.USA, 112:8290-8295, 2015

PubMed Abstract: 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 coli α2M (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."

PubMed: 26100869
DOI: 10.1073/pnas.1506538112

Experimental method

X-RAY DIFFRACTION (2.7 Å)