Mancek Mateja, Pristovsek Primoz, Jerala Roman
National Institute of Chemistry, Hajdrihova 19, Ljubljana, SI-1000, Slovenia.
Biochem Biophys Res Commun. 2002 Apr 12;292(4):880-5. doi: 10.1006/bbrc.2002.6748.
Members of the toll-like receptor family are crucial in recognition of microbial pathogens as part of innate immune response. MD-2, an accessory protein to TLR4, present on the extracellular side of the membrane is needed to initiate the signal transduction. We have identified a 15 amino acid region of human MD-2 that contains several features of other lipopolysaccharide (LPS) binding proteins and peptides. In vitro LPS neutralization by this peptide was observed and confirmed by 2D transferred NOESY NMR experiments. NMR experiments have also shown binding of the MD-2 peptide to lipoteichoic acid (LTA) but not to peptidoglycan. Furthermore this peptide inhibited growth of gram-negative and to a lower extent of some gram-positive bacteria. Our results indicate that this region of MD-2 might be responsible for binding of LPS and confirms the role of MD-2 as an accessory protein in LPS signaling bestowing the Toll receptors their specificity.
Toll样受体家族成员在识别微生物病原体作为固有免疫反应的一部分方面至关重要。MD-2是TLR4的一种辅助蛋白，位于细胞膜的胞外侧，是启动信号转导所必需的。我们已经鉴定出人类MD-2的一个15个氨基酸的区域，该区域具有其他脂多糖（LPS）结合蛋白和肽的几个特征。通过二维转移NOESY NMR实验观察并证实了该肽在体外对LPS的中和作用。NMR实验还表明MD-2肽与脂磷壁酸（LTA）结合，但不与肽聚糖结合。此外，该肽抑制革兰氏阴性菌的生长，并在较低程度上抑制一些革兰氏阳性菌的生长。我们的结果表明，MD-2的这一区域可能负责LPS的结合，并证实了MD-2作为LPS信号传导中的辅助蛋白赋予Toll受体特异性的作用。
