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 language | English (US) |
|---|---|
| Pages (from-to) | 1216-1230 |
| Number of pages | 15 |
| Journal | Biochimica et Biophysica Acta - Biomembranes |
| Volume | 1860 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 1 2018 |
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Keywords
- Dengue virus
- Envelope protein
- Fundamental interactions
- Membrane fusion
- Molecular dynamics simulations
- Neutron reflectivity
ASJC Scopus subject areas
- Biophysics
- Biochemistry
- Cell Biology
Cite this
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 journal › Article
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TY - JOUR
T1 - Insertion of Dengue E into lipid bilayers studied by neutron reflectivity and molecular dynamics simulations
AU - Vanegas, Juan M.
AU - Heinrich, Frank
AU - Rogers, David M.
AU - Carson, Bryan D.
AU - La Bauve, Sadie
AU - Vernon, Briana C.
AU - Akgun, Bulent
AU - Satija, Sushil
AU - Zheng, Aihua
AU - Kielian, Margaret
AU - Rempe, Susan B.
AU - Kent, Michael S.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
KW - Dengue virus
KW - Envelope protein
KW - Fundamental interactions
KW - Membrane fusion
KW - Molecular dynamics simulations
KW - Neutron reflectivity
UR - http://www.scopus.com/inward/record.url?scp=85042381868&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042381868&partnerID=8YFLogxK
U2 - 10.1016/j.bbamem.2018.02.012
DO - 10.1016/j.bbamem.2018.02.012
M3 - Article
C2 - 29447917
AN - SCOPUS:85042381868
VL - 1860
SP - 1216
EP - 1230
JO - Biochimica et Biophysica Acta - Biomembranes
JF - Biochimica et Biophysica Acta - Biomembranes
SN - 0005-2736
IS - 5
ER -