Eckert, Jana K. and Kim, Young J. and Kim, Jung I. and Guertler, Kathleen and Oh, Djin-Ye and Sur, Saubashya and Lundvall, Linn and Hamann, Lutz and van der Ploeg, Anke and Pickkers, Peter and Giamarellos-Bourboulis, Evangelos and Kubarenko, Andriy V. and Weber, Alexander N. and Kabesch, Michael and Kumpf, Oliver and An, Hyun-Jung and Lee, Jie-Oh and Schumann, Ralf R. (2013) The Crystal Structure of Lipopolysaccharide Binding Protein Reveals the Location of a Frequent Mutation that Impairs Innate Immunity. IMMUNITY, 39 (4). pp. 647-660. ISSN 1074-7613, 1097-4180
Full text not available from this repository. (Request a copy)Abstract
Lipopolysaccharide (LPS) binding protein (LBP) is an acute-phase protein that initiates an immune response after recognition of bacterial LPS. Here, we report the crystal structure of murine LBP at 2.9 angstrom resolution. Several structural differences were observed between LBP and the related bactericidal/permeability-increasing protein (BPI), and the LBP C-terminal domain contained a negatively charged groove and a hydrophobic "phenylalanine core." A frequent human LBP SNP (allelic frequency 0.08) affected this region, potentially generating a proteinase cleavage site. The mutant protein had a reduced binding capacity for LPS and lipopeptides. SNP carriers displayed a reduced cytokine response after in vivo LPS exposure and lower cytokine concentrations in pneumonia. In a retrospective trial, the LBP SNP was associated with increased mortality rates during sepsis and pneumonia. Thus, the structural integrity of LBP may be crucial for fighting infections efficiently, and future patient stratification might help to develop better therapeutic strategies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN; (LPS)-BINDING PROTEIN; CELL ACTIVATION; GENE POLYMORPHISMS; SEVERE SEPSIS; IN-VIVO; LPS; PHASE; MICE; RECOGNITION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Mar 2020 09:16 |
| Last Modified: | 31 Mar 2020 09:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/15840 |
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