7V3H
DENV2_NGC_Fab_C10 28degrees (3Fab:3E)
Summary for 7V3H
| Entry DOI | 10.2210/pdb7v3h/pdb |
| EMDB information | 31679 |
| Descriptor | Envelope protein E, Small envelope protein M, C10 IgG light chain variable region, ... (6 entities in total) |
| Functional Keywords | complex, antibody, virus, virus-immune system complex, virus/immune system |
| Biological source | Dengue virus type 2 (strain Thailand/NGS-C/1944) (DENV-2) More |
| Total number of polymer chains | 12 |
| Total formula weight | 265614.64 |
| Authors | Shu, B.,Zhang, S.,Victor, A.K.,Ng, T.S.,Lok, S.M. (deposition date: 2021-08-10, release date: 2021-12-29) |
| Primary citation | Lim, X.X.,Shu, B.,Zhang, S.,Tan, A.W.K.,Ng, T.S.,Lim, X.N.,Chew, V.S.,Shi, J.,Screaton, G.R.,Lok, S.M.,Anand, G.S. Human antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics. Cell, 184:6067-6080.e13, 2021 Cited by PubMed Abstract: The human monoclonal antibody (HmAb) C10 potently cross-neutralizes Zika virus (ZIKV) and dengue virus. Analysis of antibody fragment (Fab) C10 interactions with ZIKV and dengue virus serotype 2 (DENV2) particles by cryoelectron microscopy (cryo-EM) and amide hydrogen/deuterium exchange mass spectrometry (HDXMS) shows that Fab C10 binding decreases overall ZIKV particle dynamics, whereas with DENV2, the same Fab causes increased dynamics. Testing of different Fab C10:DENV2 E protein molar ratios revealed that, at higher Fab ratios, especially at saturated concentrations, the Fab enhanced viral dynamics (detected by HDXMS), and observation under cryo-EM showed increased numbers of distorted particles. Our results suggest that Fab C10 stabilizes ZIKV but that with DENV2 particles, high Fab C10 occupancy promotes E protein dimer conformational changes leading to overall increased particle dynamics and distortion of the viral surface. This is the first instance of a broadly neutralizing antibody eliciting virus-specific increases in whole virus particle dynamics. PubMed: 34852238DOI: 10.1016/j.cell.2021.11.009 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.6 Å) |
Structure validation
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