Table 3.
Experimentally characterized functional sites in Ebolavirus proteins
| Name | Residues | Function | Experimental evidence |
|---|---|---|---|
| GP | 40 | Glycosylated by host | N40D loss ability to infect119 |
| GP | 41–43, 503–511, 513, 514 | Interact with antibody | On the interacting surface with neutralizing antibody 55 |
| GP | 51, 68, 86, 99, 109,111, 113, 122, 139, 154, 159, 161, 162, 171, 176, 183–185 | Maintain the hydrophobic core structure | W86A, Y99A, Y109A, H139A, H154A, F159A, L161A, Y162A, Y171A, F176A, F183A reduce expression, reduce viral incorporation and abolish infectivity; L111A, I113A, L122A reduce viral incorporation and abolish infectivity; L51A, L68A, L184A, I185A abolish infectivity120 |
| GP | 53, 108, 121, 135, 147, 511, 556, 601, 608, 609 | Disulfide bond | C53G, C108A, C121G, C135S, C147S, C511G, C556S, C601S, C608G, C609G reduce expression and abolish infectivity119 |
| GP | 55, 85, 103, 117, 178 | Hydrophilic to maintain the structure | E85A, E103A, E178A reduce expression; E85A, E103A, D117A, E178A reduce viral incorporation; D55A, E103A, D117A, E178A loss ability to infect120 |
| GP | 529, 531–533, 535–537 | Fusion peptide | I529A, W531R, W531A, I532R, P533R, F535R, G536R, G536A, P537R loss ability to infect15 |
| GP | 57, 63, 64, 88, 95, 170 | Cell entry | L63K, L63A reduce expression; L57A, L57F, L57I, L57K, L63K, L63A, L63F, R64E, R64A, F88E, F88A, K95E, K95A, I170A, I170E loss ability to infect120 |
| VP24 | 96–98, 106–121 | Interact with STAT1 | Show reduced hydrogen exchange rate upon binding61 |
| VP24 | 113, 115, 117, 121, 124, 125, 128–131, 134–141, 184–186, 201–205, 218 | Interact with KPNA5 | On the interacting surface in crystal structure with KPNA5 (PDB id: 4U2X)56 |
| VP24 | 50, 71, 147, 187 | Adapt to new host | T50I mouse adaptation98; M71I, L147P, and T187I guinea pig adaptation97 |
| VP30 | 179, 180, 183, 197 | Activate transcription | Mutation to Ala reduces interaction with nucleocapsid; K180A, K183A, E197A block transcription activation59 |
| VP30 | 143, 146 | Phosphorylation | T143A, T143D, T146A, T146D inhibit transcription21 |
| VP35 | 239, 240, 309, 312, 319, 322, 339 | Bind dsRNA | K309A, K319A reduce dsRNA binding; F239A, H240A, R312A, R322A, K339A abolishes dsRNA binding70 |
| VP35 | 239, 240, 309, 312, 319, 322, 339 | IRF-3 inhibition | K309A, K319A reduce IRF-3 inhibition; F239A, H240A, R312A, R322A, K339A greatly reduce IRF-3 inhibition70 |
| VP35 | 235, 240 | Polymerase cofactor | F235A, H240A impair replication of mini-genome24 |
| VP35 | 312, 322, 339 | Bind DRPB76 | Mutation to alanine reduce ability to bind DRPB76107 |
| VP35 | 309, 312 | Inhibit RNAi | K309A and R312A lost the inhibition effect121 |
| VP35 | 305, 309, 312 | Inhibit PKR | Mutant any 2 to alanine abolish the inhibition122 |
| VP40 | 303–308 | Interact with Sec24C | 303–306A and 305–308A cannot interact with Sec24C, and reduce virus-like particles113 |
| VP40 | 51–54, 96–101, 212–214, 286–291, 303–308, 314–316 | Release of virus-like particles | 51–52A, 53–54A, deletion of 96–101, K212A, L213A, R214A, 286–288A, 289–291A, 303–306A, 305–308A reduce the release of virus-like particles113,123,124 |
| VP40 | 127, 129, 130, 283, 286, 293, 295, 298, 309–317 | Membrane localization | K127A, T129A, N130A, P283L, P286L, I293A, L295A, V298A and deletion of 309–317 reduce membrane localization27, 125 |
| VP40 | 226–255 | Interaction with microtubules | Deletion of 226–240 or 241–255 abolish ability to protect microtubules from depolymerization116 |
| VP40 | 213, 293, 295, 298 | Penetrate membrane | Mutation to alanine reduces membrane localization126 |