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

Hall, Kristopher, Lee, Tzong-Hsien, Daly, Norelle L., Craik, David J., and Aguilar, Marie-Isabel (2012) Gly6 of kalata B1 is critical for the selective binding to phosphatidylethanolamine membranes. Biochimica et Biophysica Acta. Biomembranes, 1818 (9). pp. 2354-2361.

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Abstract

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.

Item ID: 26999
Item Type: Article (Research - C1)
ISSN: 0005-2736
Keywords: SPR; AFM; peptide–lipid interaction; antimicrobial peptide; cyclotide; phospholipid membrane
Date Deposited: 22 May 2013 00:49
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060101 Analytical Biochemistry @ 100%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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