Conolysin-Mt: A Conus Peptide That Disrupts Cellular Membranes

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• 作者：Jason S. Biggs ; Yosef Rosenfeld ; Yechiel Shai ; B. M. Olivera
• 刊名：Biochemistry
• 出版年：2007
• 出版时间：November 6, 2007
• 年：2007
• 卷：46
• 期：44
• 页码：12586 - 12593
• 全文大小：340K
• 年卷期：v.46,no.44(November 6, 2007)
• ISSN：1520-4995

文摘

Conus venoms are estimated to comprise over 100,000 distinct pharmacologically activepeptides, the majority probably targeting ion channels. Through the characterization of a cytolytic peptidefrom the venom of Conus mustelinus, conolysin-Mt, we expand the known conopeptide mechanisms toinclude association with and destruction of cellular membranes. A new 23AA conopeptide, conolysin-Mthas potent hemolytic activity when tested on human erythrocytes. At a concentration of 0.25 M, thepeptide permeabilized both negatively charged prokaryotic (PE:PG) and zwitterionic eukaryotic (PC:cholesterol) model membranes. The affinity constants (K_A) of conolysin-Mt for PE:PG and PC:cholesterolmodel membranes were 0.9 ± 0.3 × 10⁷ and 3 ± 1 × 10⁷ M^-1, respectively. In contrast, conolysin-Mtexhibited low antimicrobial activity (MIC > 50 M) against two Escherichia coli strains, with an MICfor the Gram-positive S. aureus of 25-50 M. The specificity of conolysin-Mt for native eukaryoticmembranes is a novel feature of the peptide compared to other well-characterized cytolytic peptides suchas melittin.