Insertion of Dengue E into Lipid Bilayers Studied by Neutron Reflectivity Molecular Dynamics Simulations

Published

February 13, 2018

Author(s)

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

Abstract

The envelope (E) protein of Dengue virus rearranges to a trimeric hairpin to mediate fusion of the viral and target membranes, which 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 POPC with POPG, POPE, and cholesterol 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 cholesterol. The simulations show that tilting of the protein correlates with hydrogen bond formation between lysines located on the sides of the trimer close to the tip (K246 and K247) and nearby lipid headgroups. These hydrogen bonds provide the majority of the interaction energy whereas interactions involving the FL are a minor contribution.

Citation

BBA - Biomembranes

Volume

1860

Pub Type

Journals

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Keywords

neutron reflectometry, dengue, molecular dynamics simulation

Citation

Vanegas, J. , Heinrich, F. , Rogers, D. , Carson, B. , La Bauve, S. , Vernon, B. , Satija, S. , Zheng, A. , Kielian, M. , Rempe, S. and Kent, M. (2018), Insertion of Dengue E into Lipid Bilayers Studied by Neutron Reflectivity Molecular Dynamics Simulations, BBA - Biomembranes, [online], https://tsapps.nist.gov/publication/get_pdf.cfm?pub_id=922315 (Accessed October 9, 2025)