title: The Ebola virus protein VP40 hexamer enhances the clustering of PI(4,5)P2lipids in the plasma membrane.
abstract: The Ebola virus is a lipid-enveloped virus that obtains its lipid coat from the plasma membrane of the host cell it infects during the budding process. The Ebola virus protein VP40 localizes to the inner leaflet of the plasma membrane and forms the viral matrix, which provides the major structure for the Ebola virus particles. VP40 is initially a dimer that rearranges to a hexameric structure that mediates budding. VP40 hexamers and larger filaments have been shown to be stabilized by PI(4,5)P2in the plasma membrane inner leaflet. Reduction in the plasma membrane levels of PI(4,5)P2significantly reduce formation of VP40 oligomers and virus-like particles. We investigated the lipid-protein interactions in VP40 hexamers at the plasma membrane. We quantified lipid-lipid self-clustering by calculating the fractional interaction matrix and found that the VP40 hexamer significantly enhances the PI(4,5)P2clustering. The radial pair distribution functions suggest a strong interaction between PI(4,5)P2and the VP40 hexamer. The cationic Lys side chains are found to mediate the PIP2clustering around the protein, with cholesterol filling the space between the interacting PIP2molecules. These computational studies support recent experimental data and provide new insights into the mechanisms by which VP40 assembles at the plasma membrane inner leaflet, alters membrane curvature, and forms new virus-like particles.
authors.affiliation: Department of Physics, Florida International University, Miami, FL 33199, USA. chapagap@fiu.edu.
authors.forename: Jeevan B
authors.identifier: http://orcid.org/0000-0002-3589-0408
authors.initials: JB
authors.lastname: Gc
authors.affiliation: Department of Physics, Florida International University, Miami, FL 33199, USA. chapagap@fiu.edu and Biomolecular Science Institute, Florida International University, Miami, FL 33199, USA.
authors.forename: Bernard S
authors.initials: BS
authors.lastname: Gerstman
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine-South Bend, South Bend, IN 46617, USA and Department of Chemistry and Biochemistry, The Eck Institute for Global Health, and the Boler-Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, USA.
authors.forename: Robert V
authors.initials: RV
authors.lastname: Stahelin
authors.affiliation: Department of Physics, Florida International University, Miami, FL 33199, USA. chapagap@fiu.edu and Biomolecular Science Institute, Florida International University, Miami, FL 33199, USA.
authors.forename: Prem P
authors.initials: PP
authors.lastname: Chapagain
mesh_terms: D002462:Cell Membrane / Q000737:chemistry*; D003198:Computer Simulation; D029043:Ebolavirus; D008958:Models, Molecular; D009698:Nucleoproteins / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry*; D014758:Viral Core Proteins / Q000737:chemistry*
chemical_list: D009698:Nucleoproteins; D010743:Phospholipids; D014758:Viral Core Proteins; C084819:nucleoprotein VP40, Ebola virus