Lateral Membrane Heterogeneity Regulates Viral-Induced Membrane Fusion during HIV Entry
Abstract
1. Introduction
2. Results
2.1. Dependence of the Equilibrium Position of the Fusion Peptide Upon Incorporation Depth
2.2. Dependence of the Stalk Formation Energy Barrier on the Presence of a Raft
3. Discussion
4. Materials and Methods
4.1. Energy of the Membranes with Peptide Inclusions
4.2. Stalk Energy
Author Contributions
Acknowledgments
Conflicts of Interest
Abbreviations
HIV | human immunodeficiency virus |
TM | transmembrane (domain) |
References
- Simons, K.; Ikonen, E. Functional rafts in cell membranes. Nature 1997, 387, 569–572. [Google Scholar] [CrossRef] [PubMed]
- García-Sáez, A.J.; Chiantia, S.; Schwille, P. Effect of line tension on the lateral organization of lipid membranes. J. Biol. Chem. 2007, 282, 33537–33544. [Google Scholar] [CrossRef] [PubMed]
- Brown, D.A.; London, E. Functions of lipid rafts in biological membranes. Annu. Rev. Cell Dev. Biol. 1998, 14, 111–136. [Google Scholar] [CrossRef] [PubMed]
- Lingwood, D.; Kaiser, H.J.; Levental, I.; Simons, K. Lipid rafts as functional heterogeneity in cell membranes. Biochem. Soc. Trans. 2009, 37, 955–960. [Google Scholar] [CrossRef] [PubMed]
- Teissier, É.; Pécheur, E.I. Lipids as modulators of membrane fusion mediated by viral fusion proteins. Eur. Biophys. J. 2007, 36, 887–899. [Google Scholar] [CrossRef] [PubMed]
- Yang, S.T.; Kiessling, V.; Simmons, J.A.; White, J.M.; Tamm, L.K. HIV gp41–mediated membrane fusion occurs at edges of cholesterol-rich lipid domains. Nat. Chem. Biol. 2015, 11, 424–431. [Google Scholar] [CrossRef] [PubMed]
- Yang, S.T.; Kreutzberger, A.J.; Kiessling, V.; Ganser-Pornillos, B.K.; White, J.M.; Tamm, L.K. HIV virions sense plasma membrane heterogeneity for cell entry. Sci. Adv. 2017, 3, e1700338. [Google Scholar] [CrossRef] [PubMed]
- Kuzmin, P.I.; Akimov, S.A.; Chizmadzhev, Y.A.; Zimmerberg, J.; Cohen, F.S. Line tension and interaction energies of membrane rafts calculated from lipid splay and tilt. Biophys. J. 2005, 88, 1120–1133. [Google Scholar] [CrossRef] [PubMed]
- Galimzyanov, T.R.; Molotkovsky, R.J.; Bozdaganyan, M.E.; Cohen, F.S.; Pohl, P.; Akimov, S.A. Elastic membrane deformations govern interleaflet coupling of lipid-ordered domains. Phys. Rev. Lett. 2015, 115, 088101. [Google Scholar] [CrossRef] [PubMed]
- Galimzyanov, T.R.; Molotkovsky, R.J.; Kuzmin, P.I.; Akimov, S.A. Stabilization of bilayer structure of raft due to elastic deformations of membrane. Biol. Membr. 2011, 28, 307–314. [Google Scholar] [CrossRef]
- Galimzyanov, T.R.; Lyushnyak, A.S.; Aleksandrova, V.V.; Shilova, L.A.; Mikhalyov, I.I.; Molotkovskaya, I.M.; Akimov, S.A.; Batishchev, O.V. Line Activity of Ganglioside GM1 Regulates the Raft Size Distribution in a Cholesterol-Dependent Manner. Langmuir 2017, 33, 3517–3524. [Google Scholar] [CrossRef] [PubMed]
- Galimzyanov, T.R.; Molotkovsky, R.J.; Cohen, F.S.; Pohl, P.; Akimov, S.A. Comment on “Elastic membrane deformations govern interleaflet coupling of lipid-ordered domains” Reply. Phys. Rev. Lett. 2016, 116, 079802. [Google Scholar] [CrossRef] [PubMed]
- Perlmutter, J.D.; Sachs, J.N. Interleaflet interaction and asymmetry in phase separated lipid bilayers: Molecular dynamics simulations. J. Am. Chem. Soc. 2011, 133, 6563–6577. [Google Scholar] [CrossRef] [PubMed]
- Risselada, H.J.; Marrink, S.J. The molecular face of lipid rafts in model membranes. Proc. Natl. Acad. Sci. USA 2008, 105, 17367–17372. [Google Scholar] [CrossRef] [PubMed]
- Pantano, D.A.; Moore, P.B.; Klein, M.L.; Discher, D.E. Raft registration across bilayers in a molecularly detailed model. Soft Matter 2011, 7, 8182–8191. [Google Scholar] [CrossRef]
- Molotkovsky, R.J.; Kuzmin, P.I.; Akimov, S.A. Membrane fusion. Two possible mechanisms underlying a decrease in the fusion energy barrier in the presence of fusion proteins. Biol. Membr. 2015, 32, 79–92. [Google Scholar] [CrossRef]
- Molotkovsky, R.J.; Galimzyanov, T.R.; Jiménez-Munguía, I.; Pavlov, K.V.; Batishchev, O.V.; Akimov, S.A. Switching between Successful and Dead-End Intermediates in Membrane Fusion. Int. J. Mol. Sci. 2017, 18, 2598. [Google Scholar] [CrossRef] [PubMed]
- Chernomordik, L.V.; Kozlov, M.M. Mechanics of membrane fusion. Nat. Struct. Mol. Biol. 2008, 15, 675–683. [Google Scholar] [CrossRef] [PubMed]
- Efrat, A.; Chernomordik, L.V.; Kozlov, M.M. Point-like protrusion as a prestalk intermediate in membrane fusion pathway. Biophys. J. 2007, 92, L61–L63. [Google Scholar] [CrossRef] [PubMed]
- Kuzmin, P.I.; Zimmerberg, J.; Chizmadzhev, Y.A.; Cohen, F.S. A quantitative model for membrane fusion based on low-energy intermediates. Proc. Natl. Acad. Sci. USA 2001, 98, 7235–7240. [Google Scholar] [CrossRef] [PubMed]
- Ryham, R.J.; Klotz, T.S.; Yao, L.; Cohen, F.S. Calculating transition energy barriers and characterizing activation states for steps of fusion. Biophys. J. 2016, 110, 1110–1124. [Google Scholar] [CrossRef] [PubMed]
- Harrison, S.C. Viral membrane fusion. Nat. Struct. Mol. Biol. 2008, 15, 690–698. [Google Scholar] [CrossRef] [PubMed]
- Jahn, R.; Lang, T.; Südhof, T.C. Membrane fusion. Cell 2003, 112, 519–533. [Google Scholar] [CrossRef]
- Melikyan, G.B. HIV entry: A game of hide-and-fuse? Curr. Opin. Virol. 2014, 4, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Jakobsdottir, G.M.; Iliopoulou, M.; Nolan, R.; Alvarez, L.; Compton, A.A.; Padilla-Parra, S. On the whereabouts of HIV-1 cellular entry and its fusion ports. Trends Mol. Med. 2017, 23, 932–944. [Google Scholar] [CrossRef] [PubMed]
- Akimov, S.A.; Volynsky, P.E.; Galimzyanov, T.R.; Kuzmin, P.I.; Pavlov, K.V.; Batishchev, O.V. Pore formation in lipid membrane I: Continuous reversible trajectory from intact bilayer through hydrophobic defect to transversal pore. Sci. Rep. 2017, 7, 12152. [Google Scholar] [CrossRef] [PubMed]
- Akimov, S.A.; Volynsky, P.E.; Galimzyanov, T.R.; Kuzmin, P.I.; Pavlov, K.V.; Batishchev, O.V. Pore formation in lipid membrane II: Energy landscape under external stress. Sci. Rep. 2017, 7, 12509. [Google Scholar] [CrossRef] [PubMed]
- Tristram-Nagle, S.; Chan, R.; Kooijman, E.; Uppamoochikkal, P.; Qiang, W.; Weliky, D.P.; Nagle, J.F. HIV fusion peptide penetrates, disorders, and softens T-cell membrane mimics. J. Mol. Biol. 2010, 402, 139–153. [Google Scholar] [CrossRef] [PubMed]
- Wilen, C.B.; Tilton, J.C.; Doms, R.W. HIV: Cell binding and entry. Cold Spring Harb. Perspect. Med. 2012, 2, a006866. [Google Scholar] [CrossRef] [PubMed]
- Gallo, S.A.; Finnegan, C.M.; Viard, M.; Raviv, Y.; Dimitrov, A.; Rawat, S.S.; Puri, A.; Durell, S.; Blumenthal, R. The HIV Env-mediated fusion reaction. Biochim. Biophys. Acta 2003, 1614, 36–50. [Google Scholar] [CrossRef]
- Kielian, M.; Rey, F.A. Virus membrane-fusion proteins: More than one way to make a hairpin. Nat. Rev. Microbiol. 2006, 4, 67–76. [Google Scholar] [CrossRef] [PubMed]
- Chernomordik, L.V.; Frolov, V.A.; Leikina, E.; Bronk, P.; Zimmerberg, J. The pathway of membrane fusion catalyzed by influenza hemagglutinin: Restriction of lipids, hemifusion, and lipidic fusion pore formation. J. Cell Biol. 1998, 140, 1369–1382. [Google Scholar] [CrossRef] [PubMed]
- Bajimaya, S.; Frankl, T.; Hayashi, T.; Takimoto, T. Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses. Virology 2017, 510, 234–241. [Google Scholar] [CrossRef] [PubMed]
- Yang, Q.; Zhang, Q.; Tang, J.; Feng, W.H. Lipid rafts both in cellular membrane and viral envelope are critical for PRRSV efficient infection. Virology 2015, 484, 170–180. [Google Scholar] [CrossRef] [PubMed]
- Ohkura, T.; Momose, F.; Ichikawa, R.; Takeuchi, K.; Morikawa, Y. Influenza A virus hemagglutinin and neuraminidase mutually accelerate their apical targeting through clustering of lipid rafts. J. Virol. 2014, 88, 10039–10055. [Google Scholar] [CrossRef] [PubMed]
- Huarte, N.; Carravilla, P.; Cruz, A.; Lorizate, M.; Nieto-Garai, J.A.; Kräusslich, H.G.; Pérez-Gil, J.; Requejo-Isidro, J.; Nieva, J.L. Functional organization of the HIV lipid envelope. Sci. Rep. 2016, 6, 34190. [Google Scholar] [CrossRef] [PubMed]
- Webb, S.R.; Smith, S.E.; Fried, M.G.; Dutch, R.E. Transmembrane domains of highly pathogenic viral fusion proteins exhibit trimeric association in vitro. mSphere 2018, 3, e00047-18. [Google Scholar] [CrossRef] [PubMed]
- Vishwanathan, S.A.; Thomas, A.; Brasseur, R.; Epand, R.F.; Hunter, E.; Epand, R.M. Large changes in the CRAC segment of gp41 of HIV do not destroy fusion activity if the segment interacts with cholesterol. Biochemistry 2008, 47, 11869–11876. [Google Scholar] [CrossRef] [PubMed]
- Akimov, S.A.; Aleksandrova, V.V.; Galimzyanov, T.R.; Bashkirov, P.V.; Batishchev, O.V. Interaction of amphipathic peptides mediated by elastic membrane deformations. Biol. Membr. 2017, 34, 162–173. [Google Scholar] [CrossRef]
- Rawicz, W.; Olbrich, K.C.; McIntosh, T.; Needham, D.; Evans, E. Effect of chain length and unsaturation on elasticity of lipid bilayers. Biophys. J. 2000, 79, 328–339. [Google Scholar] [CrossRef]
- Hamm, M.; Kozlov, M.M. Elastic energy of tilt and bending of fluid membranes. Eur. Phys. J. E 2000, 3, 323–335. [Google Scholar] [CrossRef]
- Leikin, S.L.; Kozlov, M.M.; Chernomordik, L.V.; Markin, V.S.; Chizmadzhev, Y.A. Membrane fusion: Overcoming of the hydration barrier and local restructuring. J. Theor. Biol. 1987, 129, 411–425. [Google Scholar] [CrossRef]
- Rand, R.P.; Parsegian, V.A. Hydration forces between phospholipid bilayers. Biochim. Biophys. Acta 1989, 988, 351–376. [Google Scholar] [CrossRef]
- Frolov, V.A.; Zimmerberg, J. Cooperative elastic stresses, the hydrophobic effect, and lipid tilt in membrane remodeling. FEBS Lett. 2010, 584, 1824–1829. [Google Scholar] [CrossRef] [PubMed]
- Israelachvili, J.; Pashley, R. The hydrophobic interaction is long range, decaying exponentially with distance. Nature 1982, 300, 341–342. [Google Scholar] [CrossRef] [PubMed]
- Aeffner, S.; Reusch, T.; Weinhausen, B.; Salditt, T. Energetics of stalk intermediates in membrane fusion are controlled by lipid composition. Proc. Natl. Acad. Sci. USA 2012, 109, E1609–E1618. [Google Scholar] [CrossRef] [PubMed]
- Yi, L.; Fang, J.; Isik, N.; Chim, J.; Jin, T. HIV gp120-induced interaction between CD4 and CCR5 requires cholesterol-rich microenvironments revealed by live cell fluorescence resonance energy transfer imaging. Biol. Chem. 2006, 281, 35446–35453. [Google Scholar] [CrossRef] [PubMed]
- Luo, C.; Wang, K.; Liu, D.; Li, Y.; Zhao, Q. The functional roles of lipid rafts in T cell activation, immune diseases and HIV infection and prevention. Cell. Mol. Immunol. 2008, 5, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Carter, G.C.; Bernstone, L.; Sangani, D.; Bee, J.W.; Harder, T.; James, W. HIV entry in macrophages is dependent on intact lipid rafts. Virology 2009, 386, 192–202. [Google Scholar] [CrossRef] [PubMed]
- Van Wilgenburg, B.; Moore, M.D.; James, W.S.; Cowley, S.A. The productive entry pathway of HIV-1 in macrophages is dependent on endocytosis through lipid rafts containing CD4. PLoS ONE 2014, 9, e86071. [Google Scholar] [CrossRef] [PubMed]
- Leikin, S.; Parsegian, V.A.; Rau, D.C.; Rand, R.P. Hydration forces. Annu. Rev. Phys. Chem. 1993, 44, 369–395. [Google Scholar] [CrossRef] [PubMed]
- McMahon, H.T.; Gallop, J.L. Membrane curvature and mechanisms of dynamic cell membrane remodelling. Nature 2005, 438, 590–596. [Google Scholar] [CrossRef] [PubMed]
- Zimmerberg, J.; Kozlov, M.M. How proteins produce cellular membrane curvature. Nat. Rev. Mol. Cell Biol. 2006, 7, 9–19. [Google Scholar] [CrossRef] [PubMed]
- Shnyrova, A.V.; Bashkirov, P.V.; Akimov, S.A.; Pucadyil, T.J.; Zimmerberg, J.; Schmid, S.L.; Frolov, V.A. Geometric catalysis of membrane fission driven by flexible dynamin rings. Science 2013, 339, 1433–1436. [Google Scholar] [CrossRef] [PubMed]
- Martens, S.; Kozlov, M.M.; McMahon, H.T. How synaptotagmin promotes membrane fusion. Science 2007, 316, 1205–1208. [Google Scholar] [CrossRef] [PubMed]
- McMahon, H.T.; Kozlov, M.M.; Martens, S. Membrane curvature in synaptic vesicle fusion and beyond. Cell 2010, 140, 601–605. [Google Scholar] [CrossRef] [PubMed]
- Ahn, A.; Gibbons, D.L.; Kielian, M. The fusion peptide of Semliki Forest virus associates with sterol-rich membrane domains. J. Virol. 2002, 76, 3267–3275. [Google Scholar] [CrossRef] [PubMed]
- Freitas, M.S.; Gaspar, L.P.; Lorenzoni, M.; Almeida, F.C.; Tinoco, L.W.; Almeida, M.S.; Maia, L.F.; Degrève, L.; Valente, A.P.; Silva, J.L. Structure of the Ebola fusion peptide in a membrane-mimetic environment and the interaction with lipid rafts. J. Biol. Chem. 2007, 282, 27306–27314. [Google Scholar] [CrossRef] [PubMed]
- Leikin, S.; Kozlov, M.M.; Fuller, N.L.; Rand, R.P. Measured effects of diacylglycerol on structural and elastic properties of phospholipid membranes. Biophys. J. 1996, 71, 2623–2632. [Google Scholar] [CrossRef]
- Galimzyanov, T.R.; Molotkovsky, R.J.; Kheyfets, B.B.; Akimov, S.A. Energy of the interaction between membrane lipid domains calculated from splay and tilt deformations. JETP Lett. 2013, 96, 681–686. [Google Scholar] [CrossRef]
- Derjaguin, B.V. Interaction forces between hydrophobic and hydrophilic self-assembled monolayers. Kolloid Zeits. 1934, 69, 155–164. [Google Scholar] [CrossRef]
© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Molotkovsky, R.J.; Alexandrova, V.V.; Galimzyanov, T.R.; Jiménez-Munguía, I.; Pavlov, K.V.; Batishchev, O.V.; Akimov, S.A. Lateral Membrane Heterogeneity Regulates Viral-Induced Membrane Fusion during HIV Entry. Int. J. Mol. Sci. 2018, 19, 1483. https://doi.org/10.3390/ijms19051483
Molotkovsky RJ, Alexandrova VV, Galimzyanov TR, Jiménez-Munguía I, Pavlov KV, Batishchev OV, Akimov SA. Lateral Membrane Heterogeneity Regulates Viral-Induced Membrane Fusion during HIV Entry. International Journal of Molecular Sciences. 2018; 19(5):1483. https://doi.org/10.3390/ijms19051483
Chicago/Turabian StyleMolotkovsky, Rodion J., Veronika V. Alexandrova, Timur R. Galimzyanov, Irene Jiménez-Munguía, Konstantin V. Pavlov, Oleg V. Batishchev, and Sergey A. Akimov. 2018. "Lateral Membrane Heterogeneity Regulates Viral-Induced Membrane Fusion during HIV Entry" International Journal of Molecular Sciences 19, no. 5: 1483. https://doi.org/10.3390/ijms19051483
APA StyleMolotkovsky, R. J., Alexandrova, V. V., Galimzyanov, T. R., Jiménez-Munguía, I., Pavlov, K. V., Batishchev, O. V., & Akimov, S. A. (2018). Lateral Membrane Heterogeneity Regulates Viral-Induced Membrane Fusion during HIV Entry. International Journal of Molecular Sciences, 19(5), 1483. https://doi.org/10.3390/ijms19051483