title: Pushing the Envelope: Dengue Viral Membrane Coaxed into Shape by Molecular Simulations.
abstract: Dengue virus is a flavivirus responsible for millions of infections per year. Its surface contains a phospholipid bilayer, within which are embedded the envelope (E) and membrane (M) proteins, arranged with icosahedral geometry. Exposure to low pH triggers the E proteins to undergo conformational changes, which precede fusion with the host cell membrane and release of the viral genome. The flavivirus membrane exhibits significant local curvature and deformation, as revealed by cryoelectron microscopy (cryo-EM), but its precise structure and interactions with envelope components remain unclear. We now report simulations of the dengue viral particle that refine its envelope structure in unprecedented detail. Our final models are morphologically consistent with cryo-EM data, and reveal the structural basis for membrane curvature. Electrostatic interactions increased envelope complex stability; this coupling has potential functional significance in the context of the viral fusion mechanism and infective states.
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore; Bioinformatics Institute (A(∗)STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore.
authors.forename: Jan K
authors.initials: JK
authors.lastname: Marzinek
authors.affiliation: Bioinformatics Institute (A(∗)STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Holdbrook
authors.affiliation: Bioinformatics Institute (A(∗)STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore.
authors.forename: Roland G
authors.initials: RG
authors.lastname: Huber
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore; Bioinformatics Institute (A(∗)STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore. Electronic address: chandra@bii.a-star.edu.sg.
authors.forename: Chandra
authors.initials: C
authors.lastname: Verma
authors.affiliation: Department of Biological Sciences, National University of Singapore, 14 Science Drive 4, Singapore 117543, Singapore; Bioinformatics Institute (A(∗)STAR), 30 Biopolis Street, #07-01 Matrix, Singapore 138671, Singapore. Electronic address: peterjb@bii.a-star.edu.sg.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bond
mesh_terms: D001665:Binding Sites; D020285:Cryoelectron Microscopy; D003716:Dengue Virus / Q000737:chemistry* / Q000648:ultrastructure; D006863:Hydrogen-Ion Concentration; D008051:Lipid Bilayers / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D010713:Phosphatidylcholines / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D010718:Phosphatidylserines / Q000737:chemistry*; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D054730:Protein Interaction Domains and Motifs; D055672:Static Electricity; D014759:Viral Envelope Proteins / Q000737:chemistry*; D014771:Virion / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D014759:Viral Envelope Proteins; C057561:1-palmitoyl-2-oleoylphosphatidylethanolamine; C050294:1-palmitoyl-2-oleoylglycero-3-phosphoserine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine