Insertion of Dengue E into lipid bilayers studied by neutron reflectivity and molecular dynamics simulations

Juan M. Vanegas, Frank Heinrich, David M. Rogers, Bryan D. Carson, Sadie La Bauve, Briana C. Vernon, Bulent Akgun, Sushil Satija, Aihua Zheng, Margaret Kielian, Susan B. Rempe, Michael S. Kent

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The envelope (E) protein of Dengue virus rearranges to a trimeric hairpin to mediate fusion of the viral and target membranes, which is essential for infectivity. Insertion of E into the target membrane serves to anchor E and possibly also to disrupt local order within the membrane. Both aspects are likely to be affected by the depth of insertion, orientation of the trimer with respect to the membrane normal, and the interactions that form between trimer and membrane. In the present work, we resolved the depth of insertion, the tilt angle, and the fundamental interactions for the soluble portion of Dengue E trimers (sE) associated with planar lipid bilayer membranes of various combinations of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol (POPG), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), and cholesterol (CHOL) by neutron reflectivity (NR) and by molecular dynamics (MD) simulations. The results show that the tip of E containing the fusion loop (FL) is located at the interface of the headgroups and acyl chains of the outer leaflet of the lipid bilayers, in good agreement with prior predictions. The results also indicate that E tilts with respect to the membrane normal upon insertion, promoted by either the anionic lipid POPG or CHOL. The simulations show that tilting of the protein correlates with hydrogen bond formation between lysines and arginines located on the sides of the trimer close to the tip (K246, K247, and R73) and nearby lipid headgroups. These hydrogen bonds provide a major contribution to the membrane anchoring and may help to destabilize the target membrane.

Original languageEnglish (US)
Pages (from-to)1216-1230
Number of pages15
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1860
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Lipid bilayers
Dengue
Neutrons
Lipid Bilayers
Molecular Dynamics Simulation
Molecular dynamics
Membranes
Computer simulation
Hydrogen
Hydrogen bonds
Fusion reactions
Cholesterol
Lipids
Virus Internalization
Dengue Virus
Membrane Lipids
Anchors
Viruses
Glycerol
Lysine

Keywords

  • Dengue virus
  • Envelope protein
  • Fundamental interactions
  • Membrane fusion
  • Molecular dynamics simulations
  • Neutron reflectivity

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Vanegas, J. M., Heinrich, F., Rogers, D. M., Carson, B. D., La Bauve, S., Vernon, B. C., ... Kent, M. S. (2018). Insertion of Dengue E into lipid bilayers studied by neutron reflectivity and molecular dynamics simulations. Biochimica et Biophysica Acta - Biomembranes, 1860(5), 1216-1230. https://doi.org/10.1016/j.bbamem.2018.02.012

Insertion of Dengue E into lipid bilayers studied by neutron reflectivity and molecular dynamics simulations. / Vanegas, Juan M.; Heinrich, Frank; Rogers, David M.; Carson, Bryan D.; La Bauve, Sadie; Vernon, Briana C.; Akgun, Bulent; Satija, Sushil; Zheng, Aihua; Kielian, Margaret; Rempe, Susan B.; Kent, Michael S.

In: Biochimica et Biophysica Acta - Biomembranes, Vol. 1860, No. 5, 01.05.2018, p. 1216-1230.

Research output: Contribution to journalArticle

Vanegas, JM, Heinrich, F, Rogers, DM, Carson, BD, La Bauve, S, Vernon, BC, Akgun, B, Satija, S, Zheng, A, Kielian, M, Rempe, SB & Kent, MS 2018, 'Insertion of Dengue E into lipid bilayers studied by neutron reflectivity and molecular dynamics simulations', Biochimica et Biophysica Acta - Biomembranes, vol. 1860, no. 5, pp. 1216-1230. https://doi.org/10.1016/j.bbamem.2018.02.012
Vanegas, Juan M. ; Heinrich, Frank ; Rogers, David M. ; Carson, Bryan D. ; La Bauve, Sadie ; Vernon, Briana C. ; Akgun, Bulent ; Satija, Sushil ; Zheng, Aihua ; Kielian, Margaret ; Rempe, Susan B. ; Kent, Michael S. / Insertion of Dengue E into lipid bilayers studied by neutron reflectivity and molecular dynamics simulations. In: Biochimica et Biophysica Acta - Biomembranes. 2018 ; Vol. 1860, No. 5. pp. 1216-1230.
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abstract = "The envelope (E) protein of Dengue virus rearranges to a trimeric hairpin to mediate fusion of the viral and target membranes, which is essential for infectivity. Insertion of E into the target membrane serves to anchor E and possibly also to disrupt local order within the membrane. Both aspects are likely to be affected by the depth of insertion, orientation of the trimer with respect to the membrane normal, and the interactions that form between trimer and membrane. In the present work, we resolved the depth of insertion, the tilt angle, and the fundamental interactions for the soluble portion of Dengue E trimers (sE) associated with planar lipid bilayer membranes of various combinations of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-rac-glycerol (POPG), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), and cholesterol (CHOL) by neutron reflectivity (NR) and by molecular dynamics (MD) simulations. The results show that the tip of E containing the fusion loop (FL) is located at the interface of the headgroups and acyl chains of the outer leaflet of the lipid bilayers, in good agreement with prior predictions. The results also indicate that E tilts with respect to the membrane normal upon insertion, promoted by either the anionic lipid POPG or CHOL. The simulations show that tilting of the protein correlates with hydrogen bond formation between lysines and arginines located on the sides of the trimer close to the tip (K246, K247, and R73) and nearby lipid headgroups. These hydrogen bonds provide a major contribution to the membrane anchoring and may help to destabilize the target membrane.",
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AU - La Bauve, Sadie

AU - Vernon, Briana C.

AU - Akgun, Bulent

AU - Satija, Sushil

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