Gly₆ of kalata B1 is critical for the selective binding to phosphatidylethanolamine membranes

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• 作者：Kristopher Hall^a ; Tzong-Hsien Lee^a ; Norelle L. Daly^b ; David J. Craik^b ; Marie-Isabel Aguilar^a ; ^{mibel.aguilar@monash.edu}
• 关键词：AMP ; antimicrobial peptides ; CD ; circular dichroism ; CHAPS ; 3-[(cholamidopropyl)dimethyl-ammonio]-1-propane sulfonate ; DMPC ; 1 ; 2-dimyristoyl-sn-glycero-3-phosphocholine ; DMPG ; 1 ; 2-dimyristoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] ; DMPE ; 1 ; 2-dimyristoyl-
• 刊名：Biochimica et Biophysica Acta (BBA)/Biomembranes
• 出版年：2012
• 出版时间：September, 2012
• 年：2012
• 卷：1818
• 期：9
• 页码：2354-2361
• 全文大小：1129 K

文摘

The membrane interaction of the cyclotide kalata B1, an all-d-analogue and a single alanine substituted analogue (G6A), was studied by surface plasmon resonance (SPR) and atomic force microscopy (AFM). Kalata B1 showed a strong binding selectivity for dimyristoyl-phosphatidylethanolamine (DMPE) compared to dimyristoyl-phoshatidylcholine (DMPC)-containing lipids. However, when the interaction was visualized by AFM the peptide interacted with DMPC and DMPE in a similar manner. There was no apparent change in membrane morphology with either lipid, suggesting that kalata B1 does not act via a carpet-like disruption mechanism. The d-analogue showed similar binding by SPR and the same strong selectivity for DMPE, indicating that the membrane-interaction and lipid selectivity are not stereo-specific. SPR studies of the G6A analogue revealed that it interacted in a similar way to kalata B1 on the DMPC containing lipids, but showed no increased response on the DMPE containing lipids observed for kalata B1 and d-kalata B1. These results indicate that the Gly6 residue directly influences membrane binding as it is located near a putative membrane interacting hydrophobic patch. Overall, the data suggest that very small changes in amino acid composition (with no change in conformation) can influence specific self-association in combination with membrane binding and mediate the activity of kalata B1.