Figure 6

NES conservation amongst Old World alphavirus isolates and structural analysis of the CHIKV CP NES. (A) Various Old World alphavirus CP sequences were aligned using the ClustalW2-Multiple Sequence Alignment tool. The proposed NES is conserved amongst Old World alphavirus CPs (ONNVG: O’nyong-nyong virus strain G; SFV: Semliki Forest virus; MIDDV: Middelburg virus; BFV: Barmah Forest virus; SINDV: Sindbis virus). The contributing amino acids are shaded in green. Asterisks (*) indicate identical residues while colons (:) mark conserved and periods (.) semi-conserved substitutions. (B) The NES of the CHIKV CP forms a protrusion which is ideal for docking to proteins like CRM1. This NES region is colored magenta. (C) In silico docking of NES into the CRM1 NES binding site. (1) The CRM1 binding site for NESs is shown in blue and the pockets are labeled with Φ0 to Φ4. (2) The hydrophobic residues Φ0 to Φ4 that form the NES of CHIKV CP are docked into the respective binding pockets. (3) The prototypic NES of snurportin-1 docked to CRM1 as in PDB ID 3NBY is shown for comparison. (D) Superimposition graphics of CHIKV CP NES with snurportin-1 NES as generated by PyMOL. Snurportin-1 is colored in magenta and CHIKV CP in cyan. The major hydrophobic residues are marked.