Lipid Headgroup Spacing and Peptide Penetration, but Not Peptide Oligomerization, Modulate Peptide-Induced Fusion
- 8 December 1998
- journal article
- Published by American Chemical Society (ACS) in Biochemistry
- Vol. 38 (1) , 364-373
- https://doi.org/10.1021/bi981389u
Abstract
In this study, the mechanism by which an amphipathic negatively charged peptide consisting of 11 amino acids (WAE) induces fusion of liposomal phosphatidylcholine membranes is investigated. WAE-induced fusion, which only occurs when the peptide is covalently attached to the bilayer, shows a highly remarkable dependence on naturally occurring phosphatidylcholine species. The initial rate of fusion increased in the order 1-palmitoyl 2-arachidonoyl PC (PAPC) > 1-palmitoyl 2-oleoyl PC (POPC) > 1-stearoyl 2-oleoyl PC (SOPC) > dioleoyl PC (DOPC) > egg yolk PC. Interestingly, the susceptibility of the various PC species toward WAE-induced fusion matched a similar order of increase in intrinsic lipid headgroup spacing of the target membrane. The degree of spacing, in turn, was found to be related to the extent by which the fluorescence quantum yield of the Trp residue increased, which occurred upon the interaction of WAE with target membranes. Therefore, these results demonstrate an enhanced ability for WAE to engage in hydrophobic interactions when headgroup spacing increases. Thus, this latter parameter most likely regulates the degree of penetration of WAE into the target membrane. Apart from penetrating, WAE oligomerizes at the site of fusion as revealed by monitoring the self-quenching of the fluorescently derivatized lipid anchor to which WAE is attached. Clustering appears specifically related to the process of membrane fusion and not membrane aggregation. This is indicated by the fact that fusion and clustering, but not aggregation, display the same strict temperature dependence. However, evidence is presented indicating that clustering is an accompanying event rather than a prerequisite for fusion. The notion that various biologically relevant fusion phenomena are accompanied by protein clustering and the specific PC-species-dependent regulation of membrane fusion emphasize the biological significance of the peptide in serving as a model for investigating mechanisms of protein-induced fusion.Keywords
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