RRC ID 3765
Author Doan N, Gettins PG.
Title alpha-Macroglobulins are present in some gram-negative bacteria: characterization of the alpha2-macroglobulin from Escherichia coli.
Journal J Biol Chem
Abstract alpha-Macroglobulins (alphaMs) are large glycoproteins that have been identified in a wide range of vertebrate and invertebrate species and are mostly thiol ester containing proteinase inhibitors. A recent analysis of bacterial genomes ( Budd, A., Blandin, S., Levashina, E. A., and Gibson, T. J. (2004) Genome Biol. 5, R38 ) identified many alpha-macroglobulin-like sequences that appear to have been acquired by Gram-negative bacteria from their metazoan hosts. We report the first expression and characterization of such a bacterial alpha-macroglobulin, that from Escherichia coli. This is also the first alpha-macroglobulin to be characterized that is predicted to be membrane-anchored. We found that the 183-kDa protein contains an intact thiol ester, is monomeric, and is localized to the periplasmic space. Reaction with proteinase results in limited cleavage within a bait region, rapid activation of the thiol ester, cross-linking to the attacking proteinase or other available nucleophiles, and partial protection of the proteinase against macromolecular substrates. Given these properties and the co-occurrence of the alphaM gene with one for a repair transglycosylase, this suggests a possible role for bacterial alphaMs in cell defense following host attack. Such a role would make bacterial alphaMs appropriate novel targets for antibiotic drugs.
Volume 283(42)
Pages 28747-56
Published 2008-10-17
DOI 10.1074/jbc.M803127200
PII M803127200
PMID 18697741
PMC PMC2568910
MeSH Amino Acid Sequence Anti-Bacterial Agents / chemistry Cloning, Molecular Escherichia coli / metabolism* Esters / chemistry Gram-Negative Bacteria / metabolism* Humans Leukocyte Elastase / metabolism Models, Biological Molecular Sequence Data Spectrometry, Fluorescence / methods Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Sulfhydryl Compounds / chemistry alpha-Macroglobulins / chemistry* alpha-Macroglobulins / metabolism*
IF 4.106
Times Cited 17
Prokaryotes E. coli ME7986(MG1655) 2421(b2520)
INFORMATION E. coli strain