3JAU

The cryoEM map of EV71 mature viron in complex with the Fab fragment of antibody D5

Summary for 3JAU

• Entry DOI: 10.2210/pdb3jau/pdb
• EMDB information: 6366
• Descriptor: Capsid protein VP1, Heavy chain of Fab fragment variable region of antibody D5, Light chain of Fab fragment variable region of antibody D5 (3 entities in total)
• Functional Keywords: enterovirus 71(ev71), virus-antibody complex, bivalent binding, high resolution cryo-em, virus-immune system complex, virus/immune system
• Biological source: Human enterovirus; More
• Total number of polymer chains: 3
• Total formula weight: 27139.91

Authors

Fan, C.,Ye, X.H.,Ku, Z.Q.,Zuo, T.,Kong, L.L.,Zhang, C.,Shi, J.P.,Liu, Q.W.,Chen, T.,Zhang, Y.Y.,Jiang, W.,Zhang, L.Q.,Huang, Z.,Cong, Y. (deposition date: 2015-06-24, release date: 2016-02-10, Last modification date: 2024-10-09)

Primary citation

Ye, X.H.,Fan, C.,Ku, Z.Q.,Zuo, T.,Kong, L.L.,Zhang, C.,Shi, J.P.,Liu, Q.W.,Chen, T.,Zhang, Y.Y.,Jiang, W.,Zhang, L.Q.,Huang, Z.,Cong, Y.
Structural Basis for Recognition of Human Enterovirus 71 by a Bivalent Broadly Neutralizing Monoclonal Antibody
Plos Pathog., 12:e1005454-e1005454, 2016

PubMed Abstract: Enterovirus 71 (EV71) is the main pathogen responsible for hand, foot and mouth disease with severe neurological complications and even death in young children. We have recently identified a highly potent anti-EV71 neutralizing monoclonal antibody, termed D5. Here we investigated the structural basis for recognition of EV71 by the antibody D5. Four three-dimensional structures of EV71 particles in complex with IgG or Fab of D5 were reconstructed by cryo-electron microscopy (cryo-EM) single particle analysis all at subnanometer resolutions. The most critical EV71 mature virion-Fab structure was resolved to a resolution of 4.8 Å, which is rare in cryo-EM studies of virus-antibody complex so far. The structures reveal a bivalent binding pattern of D5 antibody across the icosahedral 2-fold axis on mature virion, suggesting that D5 binding may rigidify virions to prevent their conformational changes required for subsequent RNA release. Moreover, we also identified that the complementary determining region 3 (CDR3) of D5 heavy chain directly interacts with the extremely conserved VP1 GH-loop of EV71, which was validated by biochemical and virological assays. We further showed that D5 is indeed able to neutralize a variety of EV71 genotypes and strains. Moreover, D5 could potently confer protection in a mouse model of EV71 infection. Since the conserved VP1 GH-loop is involved in EV71 binding with its uncoating receptor, the scavenger receptor class B, member 2 (SCARB2), the broadly neutralizing ability of D5 might attribute to its inhibition of EV71 from binding SCARB2. Altogether, our results elucidate the structural basis for the binding and neutralization of EV71 by the broadly neutralizing antibody D5, thereby enhancing our understanding of antibody-based protection against EV71 infection.

PubMed: 26938634
DOI: 10.1371/journal.ppat.1005454

Experimental method

ELECTRON MICROSCOPY (4.8 Å)