| Structural highlights
Function
Q9II02_9FLAV Component of the viral RNA replication complex that functions in virion assembly and antagonizes the host immune response.[ARBA:ARBA00024317] Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[ARBA:ARBA00003504] Serine protease subunit NS2B: Required cofactor for the serine protease function of NS3.[PROSITE-ProRule:PRU00859]
Publication Abstract from PubMed
The human monoclonal antibody C10 exhibits extraordinary cross-reactivity, potently neutralizing Zika virus (ZIKV) and the four serotypes of dengue virus (DENV1-DENV4). Here we describe a comparative structure-function analysis of C10 bound to the envelope (E) protein dimers of the five viruses it neutralizes. We demonstrate that the C10 Fab has high affinity for ZIKV and DENV1 but not for DENV2, DENV3, and DENV4. We further show that the C10 interaction with the latter viruses requires an E protein conformational landscape that limits binding to only one of the three independent epitopes per virion. This limited affinity is nevertheless counterbalanced by the particle's icosahedral organization, which allows two different dimers to be reached by both Fab arms of a C10 immunoglobulin. The epitopes' geometric distribution thus confers C10 its exceptional neutralization breadth. Our results highlight the importance not only of paratope/epitope complementarity but also the topological distribution for epitope-focused vaccine design.
The epitope arrangement on flavivirus particles contributes to Mab C10's extraordinary neutralization breadth across Zika and dengue viruses.,Sharma A, Zhang X, Dejnirattisai W, Dai X, Gong D, Wongwiwat W, Duquerroy S, Rouvinski A, Vaney MC, Guardado-Calvo P, Haouz A, England P, Sun R, Zhou ZH, Mongkolsapaya J, Screaton GR, Rey FA Cell. 2021 Dec 9;184(25):6052-6066.e18. doi: 10.1016/j.cell.2021.11.010. Epub, 2021 Nov 30. PMID:34852239[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sharma A, Zhang X, Dejnirattisai W, Dai X, Gong D, Wongwiwat W, Duquerroy S, Rouvinski A, Vaney MC, Guardado-Calvo P, Haouz A, England P, Sun R, Zhou ZH, Mongkolsapaya J, Screaton GR, Rey FA. The epitope arrangement on flavivirus particles contributes to Mab C10's extraordinary neutralization breadth across Zika and dengue viruses. Cell. 2021 Dec 9;184(25):6052-6066.e18. doi: 10.1016/j.cell.2021.11.010. Epub, 2021 Nov 30. PMID:34852239 doi:http://dx.doi.org/10.1016/j.cell.2021.11.010
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