4HZL

Neutralizing antibody mAb#8 in complex with the Epitope II of HCV E2 envelope protein

Summary for 4HZL

• Entry DOI: 10.2210/pdb4hzl/pdb
• Descriptor: Fab heavy chain, Fab light chain, E2 envelop protein, ... (4 entities in total)
• Functional Keywords: ig domain, neutralizing antibody, immune system
• Biological source: Mus musculus (mouse); More
• Total number of polymer chains: 6
• Total formula weight: 99218.81

Authors

Deng, L.,Zhang, P. (deposition date: 2012-11-15, release date: 2013-05-01, Last modification date: 2024-11-20)

Primary citation

Deng, L.,Zhong, L.,Struble, E.,Duan, H.,Ma, L.,Harman, C.,Yan, H.,Virata-Theimer, M.L.,Zhao, Z.,Feinstone, S.,Alter, H.,Zhang, P.
Structural evidence for a bifurcated mode of action in the antibody-mediated neutralization of hepatitis C virus.
Proc.Natl.Acad.Sci.USA, 110:7418-7422, 2013

PubMed Abstract: Hepatitis C virus (HCV) envelope glycoprotein E2 has been considered as a major target for vaccine design. Epitope II, mapped between residues 427-446 within the E2 protein, elicits antibodies that are either neutralizing or nonneutralizing. The fundamental mechanism of antibody-mediated neutralization at epitope II remains to be defined at the atomic level. Here we report the crystal structure of the epitope II peptide in complex with a monoclonal antibody (mAb#8) capable of neutralizing HCV. The complex structure revealed that this neutralizing antibody engages epitope II via interactions with both the C-terminal α-helix and the N-terminal loop using a bifurcated mode of action. Our structural insights into the key determinants for the antibody-mediated neutralization may contribute to the immune prophylaxis of HCV infection and the development of an effective HCV vaccine.

PubMed: 23589879
DOI: 10.1073/pnas.1305306110

Experimental method

X-RAY DIFFRACTION (2.85 Å)