4M4D

Crystal structure of lipopolysaccharide binding protein

Summary for 4M4D

• Entry DOI: 10.2210/pdb4m4d/pdb
• Descriptor: Lipopolysaccharide-binding protein, 2-acetamido-2-deoxy-beta-D-glucopyranose, 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE (3 entities in total)
• Functional Keywords: beta barrel, immune response, lipopolysaccharide, blood, lipid binding protein
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 2
• Total formula weight: 107405.58

Authors

Eckert, J.K.,Kim, Y.J.,Kim, J.I.,Gurtler, K.,Oh, D.Y.,Ploeg, A.H.,Pickkers, P.,Lundvall, L.,Hamann, L.,Giamarellos-Bourboulis, E.,Kubarenko, A.V.,Weber, A.N.,Kabesch, M.,Kumpf, O.,An, H.J.,Lee, J.O.,Schumann, R.R. (deposition date: 2013-08-07, release date: 2013-10-30, Last modification date: 2024-11-06)

Primary citation

Eckert, J.K.,Kim, Y.J.,Kim, J.I.,Gurtler, K.,Oh, D.Y.,Sur, S.,Lundvall, L.,Hamann, L.,van der Ploeg, A.,Pickkers, P.,Giamarellos-Bourboulis, E.,Kubarenko, A.V.,Weber, A.N.,Kabesch, M.,Kumpf, O.,An, H.J.,Lee, J.O.,Schumann, R.R.
The crystal structure of lipopolysaccharide binding protein reveals the location of a frequent mutation that impairs innate immunity.
Immunity, 39:647-660, 2013

PubMed 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.

PubMed: 24120359
DOI: 10.1016/j.immuni.2013.09.005

Experimental method

X-RAY DIFFRACTION (2.909 Å)