Cholesterol Modulates Membrane Properties and the Interaction of gp41 Fusion Peptide To Promote Membrane Fusion
An envelope glycoprotein, gp41, is crucial for the entry of human immunodeficiency virus (HIV) into the host cell. The 20-23 N-terminal amino acid sequence of gp41 plays an important role in promoting fusion between viral and host cells. Interestingly, the structure and function of the fusion peptide are extremely sensitive to the characteristics of the lipid environment. In this present work, we have extensively utilized steady-state and time-resolved fluorescence spectroscopy in tandem with molecular dynamics simulation to elucidate peptide binding and peptide-induced perturbation to the membrane. We have used two depth-dependent fluorescence probes, 1,6-diphenyl-1,3,5-hexatriene (DPH) and its trimethylammonium derivative (TMA-DPH), to monitor the effect of peptide binding along the bilayer normal and have reconciled the experimental observation with the insights from the simulated molecular events. We have further monitored the effect of membrane cholesterol on peptide-induced membrane perturbation. The molecular dynamics simulation data show that the peptide alters the membrane properties in the vicinity of the peptide and it penetrates to a larger extent into the bilayer when the membrane contains cholesterol. Our results clearly elucidate that cholesterol alters the membrane physical properties in favor of membrane fusion and interaction pattern of the fusion peptide with the membrane in a concentration-dependent fashion. The role of cholesterol is specifically important as the host eukaryotic cells contain a decent amount of cholesterol that might be critical for the entry of HIV into the host cells.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:123 |
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| Enthalten in: |
The journal of physical chemistry. B - 123(2019), 33 vom: 22. Aug., Seite 7113-7122 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Meher, Geetanjali [VerfasserIn] |
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| Links: |
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| Themen: |
97C5T2UQ7J |
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| Anmerkungen: |
Date Completed 14.08.2020 Date Revised 14.08.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.jpcb.9b04577 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM29956908X |
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| 245 | 1 | 0 | |a Cholesterol Modulates Membrane Properties and the Interaction of gp41 Fusion Peptide To Promote Membrane Fusion |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a An envelope glycoprotein, gp41, is crucial for the entry of human immunodeficiency virus (HIV) into the host cell. The 20-23 N-terminal amino acid sequence of gp41 plays an important role in promoting fusion between viral and host cells. Interestingly, the structure and function of the fusion peptide are extremely sensitive to the characteristics of the lipid environment. In this present work, we have extensively utilized steady-state and time-resolved fluorescence spectroscopy in tandem with molecular dynamics simulation to elucidate peptide binding and peptide-induced perturbation to the membrane. We have used two depth-dependent fluorescence probes, 1,6-diphenyl-1,3,5-hexatriene (DPH) and its trimethylammonium derivative (TMA-DPH), to monitor the effect of peptide binding along the bilayer normal and have reconciled the experimental observation with the insights from the simulated molecular events. We have further monitored the effect of membrane cholesterol on peptide-induced membrane perturbation. The molecular dynamics simulation data show that the peptide alters the membrane properties in the vicinity of the peptide and it penetrates to a larger extent into the bilayer when the membrane contains cholesterol. Our results clearly elucidate that cholesterol alters the membrane physical properties in favor of membrane fusion and interaction pattern of the fusion peptide with the membrane in a concentration-dependent fashion. The role of cholesterol is specifically important as the host eukaryotic cells contain a decent amount of cholesterol that might be critical for the entry of HIV into the host cells | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a HIV Envelope Protein gp41 |2 NLM | |
| 650 | 7 | |a Lipid Bilayers |2 NLM | |
| 650 | 7 | |a Peptide Fragments |2 NLM | |
| 650 | 7 | |a gp41 protein, Human immunodeficiency virus 1 |2 NLM | |
| 650 | 7 | |a Cholesterol |2 NLM | |
| 650 | 7 | |a 97C5T2UQ7J |2 NLM | |
| 700 | 1 | |a Sinha, Souvik |e verfasserin |4 aut | |
| 700 | 1 | |a Pattnaik, Gourab Prasad |e verfasserin |4 aut | |
| 700 | 1 | |a Ghosh Dastidar, Shubhra |e verfasserin |4 aut | |
| 700 | 1 | |a Chakraborty, Hirak |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1021/acs.jpcb.9b04577 |3 Volltext |
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