Membrane vesiculation induced by proteins of the dengue virus envelope studied by molecular dynamics simulations

• Published in: Journal of Physics: Condensed Matter Vol. 29; no. 50; pp. 504002 - 504009
• Main Authors: de Oliveira dos Santos Soares, Ricardo, Bortot, Leandro Oliveira, van der Spoel, David, Caliri, Antonio
• Format: Journal Article Web Resource
• Language: English
• Published: England IOP Publishing 20.12.2017
• Subjects: Cell Membrane - chemistry; dengue; Dengue Virus - chemistry; envelope; GROMACS; Molecular Dynamics Simulation; Protein Structure, Secondary; simulation; Special Issue on Viral Capsids; Viral Envelope Proteins - chemistry; virus
• ISSN: 0953-8984; 1361-648X; 1361-648X; 0953-8984
• DOI: 10.1088/1361-648X/aa99c6

Biological membranes are continuously remodeled in the cell by specific membrane-shaping machineries to form, for example, tubes and vesicles. We examine fundamental mechanisms involved in the vesiculation processes induced by a cluster of envelope (E) and membrane (M) proteins of the dengue virus (DENV) using molecular dynamics simulations and a coarse-grained model. We show that an arrangement of three E-M heterotetramers (EM3) works as a bending unit and an ordered cluster of five such units generates a closed vesicle, reminiscent of the virus budding process. In silico mutagenesis of two charged residues of the anchor helices of the envelope proteins of DENV shows that Arg-471 and Arg-60 are fundamental to produce bending stress on the membrane. The fine-tuning between the size of the EM3 unit and its specific bending action suggests this protein unit is an important factor in determining the viral particle size.