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7SGT

Domain III (EDIII) of the POWV E glycoprotein

Summary for 7SGT
Entry DOI10.2210/pdb7sgt/pdb
Related7KYL
NMR InformationBMRB: 30959
DescriptorEnvelope protein E (1 entity in total)
Functional Keywordspowassan virus, nanoparticle immunogen, flavivirus, monoclonal antibody, viral protein
Biological sourceTick-borne powassan virus (strain lb)
Total number of polymer chains1
Total formula weight11182.76
Authors
Harris, R.,Cahill, S.M.,Cowburn, D. (deposition date: 2021-10-07, release date: 2022-05-18, Last modification date: 2024-10-16)
Primary citationMalonis, R.J.,Georgiev, G.I.,Haslwanter, D.,VanBlargan, L.A.,Fallon, G.,Vergnolle, O.,Cahill, S.M.,Harris, R.,Cowburn, D.,Chandran, K.,Diamond, M.S.,Lai, J.R.
A Powassan virus domain III nanoparticle immunogen elicits neutralizing and protective antibodies in mice.
Plos Pathog., 18:e1010573-e1010573, 2022
Cited by
PubMed Abstract: Powassan virus (POWV) is an emerging tick borne flavivirus (TBFV) that causes severe neuroinvasive disease. Currently, there are no approved treatments or vaccines to combat POWV infection. Here, we generated and characterized a nanoparticle immunogen displaying domain III (EDIII) of the POWV E glycoprotein. Immunization with POWV EDIII presented on nanoparticles resulted in significantly higher serum neutralizing titers against POWV than immunization with monomeric POWV EDIII. Furthermore, passive transfer of EDIII-reactive sera protected against POWV challenge in vivo. We isolated and characterized a panel of EDIII-specific monoclonal antibodies (mAbs) and identified several that potently inhibit POWV infection and engage distinct epitopes within the lateral ridge and C-C' loop of the EDIII. By creating a subunit-based nanoparticle immunogen with vaccine potential that elicits antibodies with protective activity against POWV infection, our findings enhance our understanding of the molecular determinants of antibody-mediated neutralization of TBFVs.
PubMed: 35679349
DOI: 10.1371/journal.ppat.1010573
PDB entries with the same primary citation
Experimental method
SOLUTION NMR
Structure validation

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