Περίληψη:
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.
Συγγραφείς:
Eckert, Jana K.
Kim, Young J.
Kim, Jung I.
Guertler,
Kathleen
Oh, Djin-Ye
Sur, Saubashya
Lundvall, Linn and
Hamann, Lutz
van der Ploeg, Anke
Pickkers, Peter and
Giamarellos-Bourboulis, Evangelos
Kubarenko, Andriy V.
Weber,
Alexander N.
Kabesch, Michael
Kumpf, Oliver
An, Hyun-Jung
and Lee, Jie-Oh
Schumann, Ralf R.
