4PLK

Hepatitis E Virus E2s domain (Genotype I) in complex with a neutralizing antibody 8G12

Summary for 4PLK

• Entry DOI: 10.2210/pdb4plk/pdb
• Related: 4PLJ
• Descriptor: Capsid protein, 8G12 light chain, 8G12 heavy chain (3 entities in total)
• Functional Keywords: complex, neutralizing antibody, viral protein-immune system complex, viral protein/immune system
• Biological source: Hepatitis E virus (HEV); More
• Total number of polymer chains: 12
• Total formula weight: 255248.02

Authors

Tang, X.H.,Li, S.W.,Sivaraman, J. (deposition date: 2014-05-18, release date: 2015-04-08, Last modification date: 2015-05-13)

Primary citation

Gu, Y.,Tang, X.,Zhang, X.,Song, C.,Zheng, M.,Wang, K.,Zhang, J.,Ng, M.H.,Hew, C.L.,Li, S.,Xia, N.,Sivaraman, J.
Structural basis for the neutralization of hepatitis E virus by a cross-genotype antibody
Cell Res., 25:604-620, 2015

PubMed Abstract: Hepatitis E virus (HEV), a non-enveloped, positive-sense, single-stranded RNA virus, is a major cause of enteric hepatitis. Classified into the family Hepeviridae, HEV comprises four genotypes (genotypes 1-4), which belong to a single serotype. We describe a monoclonal antibody (mAb), 8G12, which equally recognizes all four genotypes of HEV, with ∼ 2.53-3.45 nM binding affinity. The mAb 8G12 has a protective, neutralizing capacity, which can significantly block virus infection in host cells. Animal studies with genotypes 1, 3 and 4 confirmed the cross-genotype neutralizing capacity of 8G12 and its effective prevention of hepatitis E disease. The complex crystal structures of 8G12 with the HEV E2s domain (the most protruded region of the virus capsid) of the abundant genotypes 1 and 4 were determined at 4.0 and 2.3 Å resolution, respectively. These structures revealed that 8G12 recognizes both genotypes through the epitopes in the E2s dimerization region. Structure-based mutagenesis and cell-model assays with virus-like particles identified several conserved residues (Glu549, Lys554 and Gly591) that are essential for 8G12 neutralization. Moreover, the epitope of 8G12 is identified as a key epitope involved in virus-host interactions. These findings will help develop a common strategy for the prevention of the most abundant form of HEV infection.

PubMed: 25793314
DOI: 10.1038/cr.2015.34

Experimental method

X-RAY DIFFRACTION (4 Å)