7V3I

DENV2_NGC_Fab_C10 4degrees (3Fab:3E)

Summary for 7V3I

• Entry DOI: 10.2210/pdb7v3i/pdb
• EMDB information: 31680
• Descriptor: Envelope protein E, Small envelope protein M, Fab_C10_light_chain, ... (4 entities in total)
• Functional Keywords: virus, complexed, antibody, 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: 10
• Total formula weight: 238741.20

Authors

Shu, B.,Zhang, S.,Victor, A.K.,Ng, T.S.,Lok, S.M. (deposition date: 2021-08-10, release date: 2021-12-29, Last modification date: 2024-06-12)

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

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: 34852238
DOI: 10.1016/j.cell.2021.11.009

Experimental method

ELECTRON MICROSCOPY (4.4 Å)