6BZW

Structure of the Hepatitis C virus envelope glycoprotein E2 antigenic region 412-423 bound to the GL precursor of the broadly neutralizing antibody AP33

6BZW の概要

• エントリーDOI: 10.2210/pdb6bzw/pdb
• 分子名称: AP33 GL Heavy Chain, AP33 GL Light Chain, E2 AS412 peptide, ... (4 entities in total)
• 機能のキーワード: hepatitis c virus, immune system, antibodies, broadly neutralizing antibodies, rational vaccine design, as412, e2, viral protein
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 197574.96

構造登録者

Tzarum, N.,Aleman, F.,Wilson, I.A.,Law, M. (登録日: 2017-12-26, 公開日: 2018-06-20, 最終更新日: 2024-10-23)

主引用文献

Aleman, F.,Tzarum, N.,Kong, L.,Nagy, K.,Zhu, J.,Wilson, I.A.,Law, M.
Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors.
Proc. Natl. Acad. Sci. U.S.A., 115:7569-7574, 2018

PubMed Abstract: Elicitation of broadly neutralizing antibodies (bnAbs) is a leading strategy in rational vaccine design against antigenically diverse pathogens. Here, we studied a panel of monoclonal antibodies (mAbs) from mice immunized with the hepatitis C virus (HCV) envelope glycoproteins E1E2. Six of the mAbs recognize the conserved E2 antigenic site 412-423 (AS412) and cross-neutralize diverse HCV genotypes. Immunogenetic and structural analysis revealed that the antibodies originated from two different germline (GL) precursors and bind AS412 in a β-hairpin conformation. Intriguingly, the anti-HCV activity of one antibody lineage is associated with maturation of the light chain (LC), whereas the other lineage is dependent on heavy-chain (HC) maturation. Crystal structures of GL precursors of the LC-dependent lineage in complex with AS412 offer critical insights into the maturation process of bnAbs to HCV, providing a scientific foundation for utilizing the mouse model to study AS412-targeting vaccine candidates.

PubMed: 29954862
DOI: 10.1073/pnas.1802378115

実験手法

X-RAY DIFFRACTION (2.2 Å)