7A3O

Crystal structure of dengue 1 virus envelope glycoprotein in complex with the scFv fragment of the broadly neutralizing human antibody EDE1 C10

Summary for 7A3O

• Entry DOI: 10.2210/pdb7a3o/pdb
• Related: 7A3N 7A3P 7A3Q 7A3R 7A3S 7A3T 7A3U 7CTH
• Descriptor: Core protein, Single chain variable fragment (scFv) from antibody EDE1 C10, alpha-L-fucopyranose-(1-6)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: viral protein, flavivirus, class 2 fusion protein, dengue, antibody
• Biological source: Dengue virus 1; More
• Total number of polymer chains: 3
• Total formula weight: 79425.11

Authors

Sharma, A.,Vaney, M.C.,Guardado-Calvo, P.,Duquerroy, S.,Rouvinski, A.,Rey, F.A. (deposition date: 2020-08-18, release date: 2021-12-08, Last modification date: 2024-11-13)

Primary citation

Sharma, A.,Zhang, X.,Dejnirattisai, W.,Dai, X.,Gong, D.,Wongwiwat, W.,Duquerroy, S.,Rouvinski, A.,Vaney, M.C.,Guardado-Calvo, P.,Haouz, A.,England, P.,Sun, R.,Zhou, Z.H.,Mongkolsapaya, J.,Screaton, G.R.,Rey, F.A.
The epitope arrangement on flavivirus particles contributes to Mab C10's extraordinary neutralization breadth across Zika and dengue viruses.
Cell, 184:6052-6066.e18, 2021

PubMed Abstract: 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.

PubMed: 34852239
DOI: 10.1016/j.cell.2021.11.010

Experimental method

X-RAY DIFFRACTION (2.8 Å)