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Structure paper

TitleHuman antibody C10 neutralizes by diminishing Zika but enhancing dengue virus dynamics.
Journal, issue, pagesCell, Vol. 184, Issue 25, Page 6067-6080.e13, Year 2021
Publish dateDec 9, 2021
AuthorsXin-Xiang Lim / Bo Shu / Shuijun Zhang / Aaron W K Tan / Thiam-Seng Ng / Xin-Ni Lim / Valerie S-Y Chew / Jian Shi / Gavin R Screaton / Shee-Mei Lok / Ganesh S Anand /
PubMed AbstractThe 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 ...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.
External linksCell / PubMed:34852238
MethodsEM (single particle)
Resolution3.1 - 4.9 Å
Structure data

31677

7v3f

EMDB-31677, PDB-7v3f:
DENV2_NGC_Fab_C10 28degree (1Fab:3E)
Method: EM (single particle) / Resolution: 3.1 Å

31678

7v3g

EMDB-31678, PDB-7v3g:
DENV2_NGC_Fab_C10 28degrees (2Fab:3E)
Method: EM (single particle) / Resolution: 3.3 Å

31679

7v3h

EMDB-31679, PDB-7v3h:
DENV2_NGC_Fab_C10 28degrees (3Fab:3E)
Method: EM (single particle) / Resolution: 3.6 Å

31680

7v3i

EMDB-31680, PDB-7v3i:
DENV2_NGC_Fab_C10 4degrees (3Fab:3E)
Method: EM (single particle) / Resolution: 4.4 Å

31681

7v3j

EMDB-31681, PDB-7v3j:
DENV2:F(ab')2-local
Method: EM (single particle) / Resolution: 4.9 Å

EMDB-31682:
DENV2_NGC_F(ab')2
Method: EM (single particle) / Resolution: 3.43 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • dengue virus type 2 (strain thailand/ngs-c/1944)
  • Dengue virus 2 Thailand/NGS-C/1944
  • homo sapiens (human)
KeywordsVIRUS / virus complexed with antibody / VIRUS/IMMUNE SYSTEM / VIRUS-IMMUNE SYSTEM complex / complex / antibody / complexed / IMMUNE SYSTEM/VIRUS / IMMUNE SYSTEM-VIRUS complex

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