4M4D

Crystal structure of lipopolysaccharide binding protein

4M4D の概要

• エントリーDOI: 10.2210/pdb4m4d/pdb
• 分子名称: Lipopolysaccharide-binding protein, 2-acetamido-2-deoxy-beta-D-glucopyranose, 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE (3 entities in total)
• 機能のキーワード: beta barrel, immune response, lipopolysaccharide, blood, lipid binding protein
• 由来する生物種: Mus musculus (mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 107405.58

構造登録者

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. (登録日: 2013-08-07, 公開日: 2013-10-30, 最終更新日: 2024-11-06)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.909 Å)