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Title: Molecular basis of endosomal-membrane association for the dengue virus envelope protein

Abstract

Dengue virus is coated by an icosahedral shell of 90 envelope protein dimers that convert to trimers at low pH and promote fusion of its membrane with the membrane of the host endosome. We provide the first estimates for the free energy barrier and minimum for two key steps in this process: host membrane bending and protein–membrane binding. Both are studied using complementary membrane elastic, continuum electrostatics and all-atom molecular dynamics simulations. The predicted host membrane bending required to form an initial fusion stalk presents a 22–30 kcal/mol free energy barrier according to a constrained membrane elastic model. Combined continuum and molecular dynamics results predict a 15 kcal/mol free energy decrease on binding of each trimer of dengue envelope protein to a membrane with 30% anionic phosphatidylglycerol lipid. The bending cost depends on the preferred curvature of the lipids composing the host membrane leaflets, while the free energy gained for protein binding depends on the surface charge density of the host membrane. The fusion loop of the envelope protein inserts exactly at the level of the interface between the membrane's hydrophobic and head-group regions. As a result, the methods used in this work provide a means for further characterization ofmore » the structures and free energies of protein-assisted membrane fusion.« less

Authors:
 [1];  [1];  [1]
  1. Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)
Publication Date:
Research Org.:
Sandia National Laboratories (SNL), Albuquerque, NM, and Livermore, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1242426
Alternate Identifier(s):
OSTI ID: 1214661
Grant/Contract Number:  
AC04-94AL85000
Resource Type:
Published Article
Journal Name:
Biochimica et Biophysica Acta. Biomembranes
Additional Journal Information:
Journal Volume: 1848; Journal Issue: 4; Journal ID: ISSN 0005-2736
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; fusion; free energy; multi-scale models; membrane bending

Citation Formats

Rogers, David M., Kent, Michael S., and Rempe, Susan B. Molecular basis of endosomal-membrane association for the dengue virus envelope protein. United States: N. p., 2015. Web. doi:10.1016/j.bbamem.2014.12.018.
Rogers, David M., Kent, Michael S., & Rempe, Susan B. Molecular basis of endosomal-membrane association for the dengue virus envelope protein. United States. doi:10.1016/j.bbamem.2014.12.018.
Rogers, David M., Kent, Michael S., and Rempe, Susan B. Fri . "Molecular basis of endosomal-membrane association for the dengue virus envelope protein". United States. doi:10.1016/j.bbamem.2014.12.018.
@article{osti_1242426,
title = {Molecular basis of endosomal-membrane association for the dengue virus envelope protein},
author = {Rogers, David M. and Kent, Michael S. and Rempe, Susan B.},
abstractNote = {Dengue virus is coated by an icosahedral shell of 90 envelope protein dimers that convert to trimers at low pH and promote fusion of its membrane with the membrane of the host endosome. We provide the first estimates for the free energy barrier and minimum for two key steps in this process: host membrane bending and protein–membrane binding. Both are studied using complementary membrane elastic, continuum electrostatics and all-atom molecular dynamics simulations. The predicted host membrane bending required to form an initial fusion stalk presents a 22–30 kcal/mol free energy barrier according to a constrained membrane elastic model. Combined continuum and molecular dynamics results predict a 15 kcal/mol free energy decrease on binding of each trimer of dengue envelope protein to a membrane with 30% anionic phosphatidylglycerol lipid. The bending cost depends on the preferred curvature of the lipids composing the host membrane leaflets, while the free energy gained for protein binding depends on the surface charge density of the host membrane. The fusion loop of the envelope protein inserts exactly at the level of the interface between the membrane's hydrophobic and head-group regions. As a result, the methods used in this work provide a means for further characterization of the structures and free energies of protein-assisted membrane fusion.},
doi = {10.1016/j.bbamem.2014.12.018},
journal = {Biochimica et Biophysica Acta. Biomembranes},
number = 4,
volume = 1848,
place = {United States},
year = {2015},
month = {1}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1016/j.bbamem.2014.12.018

Citation Metrics:
Cited by: 7 works
Citation information provided by
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