Oligomerization and polymerization of the filovirus matrix protein VP40

• Published in: Virology (New York, N.Y.) Vol. 312; no. 2; pp. 359 - 368
• Main Authors: Timmins, Joanna, Schoehn, Guy, Kohlhaas, Christine, Klenk, Hans-Dieter, Ruigrok, Rob W.H, Weissenhorn, Winfríed
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2003
• Subjects: Ebola virus; Ebolavirus - chemistry; Ebolavirus - metabolism; Filovirus; Gene Expression Regulation, Viral; Marburg virus; Models, Molecular; Nucleoproteins - chemistry; Nucleoproteins - metabolism; Oligomerization; Protein Conformation; Protein Folding; Static Electricity; Viral Core Proteins - chemistry; Viral Core Proteins - metabolism; Virus assembly; VP40; Ebola virus; Oligomerization; Virus assembly; Filovirus; Marburg virus; VP40
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/S0042-6822(03)00260-5

The matrix protein VP40 from Ebola virus plays an important role in the assembly process of virus particles by interacting with cellular factors, cellular membranes, and the ribonuclearprotein particle complex. Here we show that the N-terminal domain of VP40 folds into a mixture of two different oligomeric states in vitro, namely hexameric and octameric ringlike structures, as detected by gel filtration chromatography, chemical cross-linking, and electron microscopy. Octamer formation depends largely on the interaction with nucleic acids, which in turn confers in vitro SDS resistance. Refolding experiments with a nucleic acid free N-terminal domain preparation reveal a mostly dimeric form of VP40, which is transformed into an SDS resistant octamer upon incubation with E. coli nucleic acids. In addition, we demonstrate that the N-terminal domain of Marburg virus VP40 also folds into ringlike structures, similar to Ebola virus VP40. Interestingly, Marburg virus VP40 rings reveal a high tendency to polymerize into rods composed of stacked rings. These results may suggest distinct roles for different oligomeric forms of VP40 in the filovirus life cycle.