ArticleProceedings of the National Academy of Sciences of the United States of America2015
Structural and functional insights into Escherichia coli α2-macroglobulin endopeptidase snap-trap inhibition.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 38 citations in OpenAlex.
- Review
- Isolation and Endopeptidase Inhibition of Human α 2-Macroglobulin.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Genome-Wide Screen using Escherichia coli Keio knockout mutant line reveals genes related to the antimicrobial properties of trans-Cinnamic Acid.World journal of microbiology & biotechnology · 2025Article
- Evolution of protease activation and specificity via alpha-2-macroglobulin-mediated covalent capture.Nature communications · 2023Article
- Cryo-EM structures reveal the dynamic transformation of human alpha-2-macroglobulin working as a protease inhibitor.Science China. Life sciences · 2022Article
- Cryo-EM structures of human A2ML1 elucidate the protease-inhibitory mechanism of the A2M family.Nature communications · 2022Article
- Cryo-EM structures show the mechanistic basis of pan-peptidase inhibition by human αProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural Mechanics of the Alpha-2-Macroglobulin Transformation.Journal of molecular biology · 2022Article
- Structural and evolutionary insights into astacin metallopeptidases.Frontiers in molecular biosciences · 2022Article
- Protein folding modulates the chemical reactivity of a Gram-positive adhesin.Nature chemistry · 2021Article
- A Unique Gene Module inFrontiers in microbiology · 2021Article
- αThe Journal of biological chemistry · 2020Article
- Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS.Gut · 2020Article
- Recombinant production of human αScientific reports · 2019Article
- Comparative Genome Analysis and Evaluation of Probiotic Characteristics ofKorean journal for food science of animal resources · 2018Article
- Assembly of an atypical α-macroglobulin complex from Pseudomonas aeruginosa.Scientific reports · 2018Article
- A structure-derived snap-trap mechanism of a multispecific serpin from the dysbiotic human oral microbiome.The Journal of biological chemistry · 2017Article
- Mechanical forces regulate the reactivity of a thioester bond in a bacterial adhesin.The Journal of biological chemistry · 2017Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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."
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.