Aggregation of Cateslytin β-Sheets on Negatively Charged Lipids Promotes Rigid Membrane Domains. A New Mode of Action for Antimicrobial Peptides?

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• 作者：Frantz Jean-Franç ; ois ; Sabine Castano ; Bernard Desbat ; Beno&#xee ; t Odaert ; Michel Roux ; Marie-Hé ; lè ; ne Metz-Boutigue ; Erick J. Dufourc
• 刊名：Biochemistry
• 出版年：2008
• 出版时间：June 17, 2008
• 年：2008
• 卷：47
• 期：24
• 页码：6394 - 6402
• 全文大小：1175K
• 年卷期：v.47,no.24(June 17, 2008)
• ISSN：1520-4995

文摘

Cateslytin, a positively charged (5+) arginine-rich antimicrobial peptide (bCgA, RSMRLSFRARGYGFR), was chemically synthesized and studied against membranes that mimic bacterial or mammalian systems. Circular dichroism, polarized attenuated total reflection infrared spectroscopy, ¹H high-resolution MAS NMR, and ²H and ³¹P solid state NMR were used to follow the interaction from peptide and membrane points of view. Cateslytin, which is unstructured in solution, is converted into antiparallel β-sheets that aggregate mainly flat at the surface of negatively charged bacterial mimetic membranes. Arginine residues are involved in the binding to negatively charged lipids. Following the interaction of the cateslytin peptide, rigid and thicker membrane domains enriched in negatively charged lipids are found. Much less interaction is detected with neutral mammalian model membranes, as reflected by only minor percentages of β-sheets or helices in the peptide secondary structure. No membrane destruction was detected for both bacterial and mammalian model membranes. A molecular model is proposed in which zones of different rigidity and thickness bring about phase boundary defects that ultimately lead to permeability induction and peptide crossing through bacterial membranes.