6WO5

Structure of Hepatitis C Virus Envelope Glycoprotein E2 core from genotype 1a bound to neutralizing antibody 212.1.1 and non neutralizing antibody E1

Summary for 6WO5

• Entry DOI: 10.2210/pdb6wo5/pdb
• Descriptor: Fab E1 heavy chain, beta-D-mannopyranose, Fab E1 light chain, ... (11 entities in total)
• Functional Keywords: hcv, broadly neutralizing antibodies, bnabs, e2 core, ighv1-69, immune system, immune system-viral protein complex, immune system/viral protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 236711.46

Authors

Tzarum, N.,Wilson, I.A.,Law, M. (deposition date: 2020-04-24, release date: 2020-08-19, Last modification date: 2023-10-18)

Primary citation

Tzarum, N.,Giang, E.,Kadam, R.U.,Chen, F.,Nagy, K.,Augestad, E.H.,Velazquez-Moctezuma, R.,Keck, Z.Y.,Hua, Y.,Stanfield, R.L.,Dreux, M.,Prentoe, J.,Foung, S.K.H.,Bukh, J.,Wilson, I.A.,Law, M.
An alternate conformation of HCV E2 neutralizing face as an additional vaccine target.
Sci Adv, 6:eabb5642-eabb5642, 2020

PubMed Abstract: To achieve global elimination of hepatitis C virus (HCV), an effective cross-genotype vaccine is needed. The HCV envelope glycoprotein E2 is the main target for neutralizing antibodies (nAbs), which aid in HCV clearance and protection. E2 is structurally flexible and functions in engaging host receptors. Many nAbs bind to the "neutralizing face" on E2, including several broadly nAbs encoded by the germline gene family that bind to a similar conformation (A) of this face. Here, a previously unknown conformation (B) of the neutralizing face is revealed in crystal structures of two of four additional E2-V1-69 nAb complexes. In this conformation, the E2 front-layer region is displaced upon antibody binding, exposing residues in the back layer for direct antibody interaction. This E2 B structure may represent another conformational state in the viral entry process that is susceptible to antibody neutralization and thus provide a new target for rational vaccine development.

PubMed: 32754640
DOI: 10.1126/sciadv.abb5642

Experimental method

X-RAY DIFFRACTION (2.619 Å)