Figures & data
Figure 1. Structure of the EBOV VP40 dimers. The recent dimeric structure of VP40 (PDB ID: 4LDB Citation[17]) is shown with the N-terminal domain in gray and the C-terminal domain in black. The VP40 N-terminal domain dimeric interface involves residues 52 – 65 and 108 – 117 both of which are part of alpha helices. These interactions have little H-bonding and are mostly hydrophobic in nature. Specifically residues involved are Ala55, His61, Phe108, Thr112, Ala113, Met116, and Leu117 where Leu117 seems to be of key importance. The inset shows a close-up of the dimeric interface with Leu117 shown in magenta. Mutation of Leu117 disrupts formation of VP40 dimers and abrogates viral budding.
![Figure 1. Structure of the EBOV VP40 dimers. The recent dimeric structure of VP40 (PDB ID: 4LDB Citation[17]) is shown with the N-terminal domain in gray and the C-terminal domain in black. The VP40 N-terminal domain dimeric interface involves residues 52 – 65 and 108 – 117 both of which are part of alpha helices. These interactions have little H-bonding and are mostly hydrophobic in nature. Specifically residues involved are Ala55, His61, Phe108, Thr112, Ala113, Met116, and Leu117 where Leu117 seems to be of key importance. The inset shows a close-up of the dimeric interface with Leu117 shown in magenta. Mutation of Leu117 disrupts formation of VP40 dimers and abrogates viral budding.](/cms/asset/509943cf-35f8-42eb-bbd0-91b5c32c667b/iett_a_863877_f0001_b.jpg)
Figure 2. Potentially druggable sites of VP40. The VP40 dimer is shown with some potential sites of inhibition to block viral budding. The VP40 dimeric interface is shown in magenta and the C-terminal domain hexameric interface mainly attributed to Met241 and Ile307 is shown in green Citation[17]. Disruption of the hexameric interface through mutagenesis reduces viral budding from the plasma membrane. The cationic patch exposed on the same interface of the dimer is shown in blue and mainly consists of Lys224, Lys225, Lys274, and Lys275 Citation[17], which may interact through electrostatic interactions with the anionic inner leaflet of the plasma membrane. Mutation of these Lys residues greatly reduces viral budding. A hydrophobic loop shown in red has been shown to penetrate into the plasma membrane Citation[21,23], a necessary step for viral budding. Still unknown is the orientation of the C-terminal domain at the plasma membrane interface with respect to the cationic patch and the hydrophobic loop.
![Figure 2. Potentially druggable sites of VP40. The VP40 dimer is shown with some potential sites of inhibition to block viral budding. The VP40 dimeric interface is shown in magenta and the C-terminal domain hexameric interface mainly attributed to Met241 and Ile307 is shown in green Citation[17]. Disruption of the hexameric interface through mutagenesis reduces viral budding from the plasma membrane. The cationic patch exposed on the same interface of the dimer is shown in blue and mainly consists of Lys224, Lys225, Lys274, and Lys275 Citation[17], which may interact through electrostatic interactions with the anionic inner leaflet of the plasma membrane. Mutation of these Lys residues greatly reduces viral budding. A hydrophobic loop shown in red has been shown to penetrate into the plasma membrane Citation[21,23], a necessary step for viral budding. Still unknown is the orientation of the C-terminal domain at the plasma membrane interface with respect to the cationic patch and the hydrophobic loop.](/cms/asset/a9d5ea5f-f912-4663-ae76-0c99dc3a4277/iett_a_863877_f0002_b.jpg)