2024-03-29T11:21:53Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/99982023-10-25T09:32:31Zcom_20.500.12105_2060com_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_2061
00925njm 22002777a 4500
dc
Garcia-Ferrer, Irene
author
Arêde, Pedro
author
Gómez-Blanco, Josué
author
Luque, Daniel
author
Duquerroy, Stephane
author
Castón, José R
author
Goulas, Theodoros
author
Gomis-Rüth, F Xavier
author
2015-07-07
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."
Proc Natl Acad Sci U S A. 2015 Jul 7;112(27):8290-5.
0027-8424
http://hdl.handle.net/20.500.12105/9998
26100869
10.1073/pnas.1506538112
1091-6490
Proceedings of the National Academy of Sciences of the United States of America
X-ray crystal structure
Conformational rearrangement
Cryo-electron microscopy
Gut microbiome
Protein inhibitor
Structural and functional insights into Escherichia coli α2-macroglobulin endopeptidase snap-trap inhibition