The Molecular Mechanism of Interaction between Sushi Peptide and Pseudomonas Endotoxin  

作　　者：Peng Li Miao Sun Thorsten Wohland Bow Ho Jeak Ling Ding 

机构地区：[1]Departments of Biological Sciences,National University of Singapore, Singapore 1175431,Singapore [2]Departments of Chemistry , National University of Singapore, Singapore 117543, Singapore [3]Departments of Microbiology, National University of Singapore, Singapore 117543, Singapore [4]Departments of Biological Sciences and Microbiology, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore

出　　处：《Cellular & Molecular Immunology》2006年第1期21-28,共8页中国免疫学杂志（英文版）

摘　　要：Septic shock is caused by Gram-negative bacterial infection. Lipopolysaccharide （LPS） is the bioactive molecule present on the outer membrane of the Gram-negative bacteria. It is generally thought that LPS interacts with sensors on the host cell membrane to activate the intracellular signaling pathway resulting in the overproduction of cytokines such as TNF-α This causes inflammation and ultimately, septic shock. Lipid A is the pharmacophore of the LPS molecule. Thus, developing bio-molecules which are capable of binding LPS at high affinity, especially to the lipid A moiety is an efficient way to neutralize the LPS toxicity. Factor C, a serine protease in the horseshoe crab ameobocytes, is sensitive to trace levels of LPS. We have derived Sushi peptides from the LPS-binding domains of Factor C. Our earlier study showed that the Sushi peptides inhibit LPS-induced septic shock in mice. Here, we demonstrate that the molecular interaction between LPS and Sushi 1 peptide is supported by the hydrophobic interaction between the lipid tail of LPS and Sushi 1 peptide. Furthermore, in the presence of LPS, the peptide transitions from a random structure into an α-helical conformation and it disrupts LPS aggregates, hence, neutralizing the LPS toxicity.Septic shock is caused by Gram-negative bacterial infection. Lipopolysaccharide （LPS） is the bioactive molecule present on the outer membrane of the Gram-negative bacteria. It is generally thought that LPS interacts with sensors on the host cell membrane to activate the intracellular signaling pathway resulting in the overproduction of cytokines such as TNF-α This causes inflammation and ultimately, septic shock. Lipid A is the pharmacophore of the LPS molecule. Thus, developing bio-molecules which are capable of binding LPS at high affinity, especially to the lipid A moiety is an efficient way to neutralize the LPS toxicity. Factor C, a serine protease in the horseshoe crab ameobocytes, is sensitive to trace levels of LPS. We have derived Sushi peptides from the LPS-binding domains of Factor C. Our earlier study showed that the Sushi peptides inhibit LPS-induced septic shock in mice. Here, we demonstrate that the molecular interaction between LPS and Sushi 1 peptide is supported by the hydrophobic interaction between the lipid tail of LPS and Sushi 1 peptide. Furthermore, in the presence of LPS, the peptide transitions from a random structure into an α-helical conformation and it disrupts LPS aggregates, hence, neutralizing the LPS toxicity.

关 键 词：septic shock Sushi 1 peptide Factor C Pseudomonas endotoxin/LPS LPS binding electrostatic and hydrophobic interaction 

分 类 号：R378[医药卫生—病原生物学]