The crystal structure of lipopolysaccharide binding protein reveals the location of a frequent mutation that impairs innate immunity - PubMed (original) (raw)
. 2013 Oct 17;39(4):647-60.
doi: 10.1016/j.immuni.2013.09.005. Epub 2013 Oct 10.
Young J Kim, Jung I Kim, Kathleen Gürtler, Djin-Ye Oh, Saubashya Sur, Linn Lundvall, Lutz Hamann, Anke van der Ploeg, Peter Pickkers, Evangelos Giamarellos-Bourboulis, Andriy V Kubarenko, Alexander N Weber, Michael Kabesch, Oliver Kumpf, Hyun-Jung An, Jie-Oh Lee, Ralf R Schumann
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- PMID: 24120359
- DOI: 10.1016/j.immuni.2013.09.005
Free article
The crystal structure of lipopolysaccharide binding protein reveals the location of a frequent mutation that impairs innate immunity
Jana K Eckert et al. Immunity. 2013.
Free article
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 Å 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.
Copyright © 2013 Elsevier Inc. All rights reserved.
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