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Gly(6) of kalata B1 is critical for the selective binding to phosphatidylethanolamine membranes.
- Source :
-
Biochimica et biophysica acta [Biochim Biophys Acta] 2012 Sep; Vol. 1818 (9), pp. 2354-61. Date of Electronic Publication: 2012 Apr 17. - Publication Year :
- 2012
-
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.<br /> (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Cell Membrane metabolism
Circular Dichroism
Dimyristoylphosphatidylcholine chemistry
Disulfides chemistry
Dose-Response Relationship, Drug
Kinetics
Lipids chemistry
Liposomes chemistry
Membranes, Artificial
Microscopy, Atomic Force methods
Molecular Sequence Data
Protein Binding
Protein Structure, Secondary
Surface Plasmon Resonance
Time Factors
Cyclotides chemistry
Phosphatidylethanolamines chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 0006-3002
- Volume :
- 1818
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Biochimica et biophysica acta
- Publication Type :
- Academic Journal
- Accession number :
- 22538355
- Full Text :
- https://doi.org/10.1016/j.bbamem.2012.04.007