Role of Membrane Stretch in Adsorption of Antiviral Peptides onto Lipid Membranes and Membrane Pore Formation
Many medically important viruses are enveloped viruses, which are surrounded by a structurally conserved, host-derived lipid membrane coating. Agents that target and disrupt this membrane coating could potentially function as broad-spectrum antiviral drugs. The amphipathic α-helical (AH) peptide der...
| Veröffentlicht in: | Langmuir : the ACS journal of surfaces and colloids. - 1985. - 37(2021), 45 vom: 16. Nov., Seite 13390-13398 |
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| 1. Verfasser: | |
| Weitere Verfasser: | , , |
| Format: | Online-Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2021
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| Zugriff auf das übergeordnete Werk: | Langmuir : the ACS journal of surfaces and colloids |
| Schlagworte: | Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Antiviral Agents Lipid Bilayers Lipids Peptides |
| Zusammenfassung: | Many medically important viruses are enveloped viruses, which are surrounded by a structurally conserved, host-derived lipid membrane coating. Agents that target and disrupt this membrane coating could potentially function as broad-spectrum antiviral drugs. The amphipathic α-helical (AH) peptide derived from the N-terminus of the hepatitis C virus NS5A protein is one such candidate and has been demonstrated to be able to selectively rupture lipid vesicles in the size range of viruses (<160 nm diameter). However, the mechanism underlying this membrane curvature selectivity remains elusive. In this study, we have performed molecular dynamics simulations to study the binding of the AH peptide to model membranes that are stretched to resemble the looser lipid headgroup packing present on highly curved outer membranes of nanoscale vesicles. We found that the AH peptide binds more favorably to membranes that are stretched. In addition, a tetrameric placement of peptides across the membrane induced stable pore formation in the stretched membrane. Thus, our results suggest that the AH peptide senses the high curvature of nanoscale vesicles via the enhanced exposure of lipid packing defects induced by membrane area strain |
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| Beschreibung: | Date Completed 27.01.2022 Date Revised 27.01.2022 published: Print-Electronic Citation Status MEDLINE |
| ISSN: | 1520-5827 |
| DOI: | 10.1021/acs.langmuir.1c02067 |