化学生物学课题组在J Biol Chem杂志发表研究论文

 

化学生物学课题组王义鹏副教授与大连理工大学生命科学与技术学院等单位合作,在天然活性多肽的发掘与应用方面取得新进展,在J Biol Chem (IF=4.6)杂志发表论文。
 
Identification and Characterization of the First Cathelicidin from Sea Snakes with Potent Antimicrobial and Anti-inflammatory Activity, and Special Mechanism.
Lin Wei, Jiuxiang Gao, Shumin Zhang, Sijin Wu, Zeping Xie, Guiying Ling, Yiqun Kuang, Yongliang Yang, Haining Yu*, and Yipeng Wang*
 
J Biol Chem 2015, in press, DOI: 10.1074/jbc.M115.642645.
 
ABSTRACT: Cathelicidins are a family of gene-encoded peptide effectors of innate immunity found exclusively in vertebrates. They play pivotal roles in host immune defense against microbial invasions. Dozens of cathelicidins have been identified from several vertebrate species. However, no cathelicidin from marine reptiles has been characterized before. Here we report the identification and characterization of a novel cathelicidin (Hc-CATH) from the sea snake Hydrophis cyanocinctus. Hc-CATH is composed of 30 amino acids and the sequence is KFFKRLLKSVRRAVKKFRKKPRLIGLSTLL. Circular dichroism spectroscopy and structure modeling analysis indicated that Hc-CATH mainly assumes an amphipathic alpha-helical conformation in bacterial membrane-mimetic solutions. It possesses potent, broad-spectrum and rapid antimicrobial activity. Meanwhile, it is highly stable and shows low cytotoxicity toward mammalian cells.The microbial killing activity of Hc-CATH is executed through the disruption of cell membrane and lysis of bacterial cells. Besides, Hc-CATH exhibited potent anti-inflammatory activity by inhibiting the LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α, IL-1β and IL-6. Hc-CATH could directly bind with LPS to neutralize its toxicity, and it also could bind to Toll-like receptor 4 (TLR4/MD2 complex), which therefore inhibits the binding of LPS to TLR4/MD2 complex and the subsequent activation of LPS-induced inflammatory response pathways. Taken together, our study demonstrates that Hc-CATH, the first cathelicidin from sea snake with both antimicrobial and anti-inflammatory activity, is a potent candidate for the development of peptide antibiotics.