biostudies-literatureMalojcic GNIAID NIH HHSNIGMS NIH HHS9467-72https://www.ebi.ac.uk/biostudies/studies/S-EPMC4084488biostudies-literatureUnknown111(26)The assembly of lipopolysaccharide (LPS) on the surface of Gram-negative bacterial cells is essential for their viability and is achieved by the seven-protein LPS transport (Lpt) pathway. The outer membrane (OM) lipoprotein LptE and the β-barrel membrane protein LptD form a complex that assembles LPS into the outer leaflet of the OM. We report a crystal structure of the Escherichia coli OM lipoprotein LptE at 2.34 Å. The structure reveals homology to eukaryotic LPS-binding proteins and allowed for the prediction of an LPS-binding site, which was confirmed by genetic and biophysical experiments. Specific point mutations at this site lead to defects in OM biogenesis. We show that wild-type LptE disrupts LPS-LPS interactions in vitro and that these mutations decrease the ability of LptE to diProceedings of the National Academy of Sciences of the United States of AmericaLptE binds to and alters the physical state of LPS to catalyze its assembly at the cell surface.PMC4084488R01 GM034821P41 GM111244R37 GM034821AI081059R01 AI081059GM034821Silhavy TJGrabowicz MAndres DKahne DMalojcic GRuiz NGeorge AHfalseLptE binds to and alters the physical state of LPS to catalyze its assembly at the cell surface.The assembly of lipopolysaccharide (LPS) on the surface of Gram-negative bacterial cells is essential for their viability and is achieved by the seven-protein LPS transport (Lpt) pathway. The outer membrane (OM) lipoprotein LptE and the β-barrel membrane protein LptD form a complex that assembles LPS into the outer leaflet of the OM. We report a crystal structure of the Escherichia coli OM lipoprotein LptE at 2.34 Å. The structure reveals homology to eukaryotic LPS-binding proteins and allowed for the prediction of an LPS-binding site, which was confirmed by genetic and biophysical experiments. Specific point mutations at this site lead to defects in OM biogenesis. We show that wild-type LptE disrupts LPS-LPS interactions in vitro and that these mutations decrease the ability of LptE to di2014-01-01T00:00:00Z2014 Jul2026-05-03T15:30:13.822Z2019-03-27T01:31:32ZS-EPMC40844882493878510.1073/pnas.1402746111