6BKB

Structure of Hepatitis C Virus Envelope Glycoprotein E2 core from genotype 6a bound to broadly neutralizing antibody AR3A

Summary for 6BKB

• Entry DOI: 10.2210/pdb6bkb/pdb
• Descriptor: Fab AR3A heavy chain, Polyprotein, Fab AR3A light chain, ... (6 entities in total)
• Functional Keywords: hcv, broadly neutralizing antibodies, bnabs, e2 core, ighv1-69, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 69673.65

Authors

Tzarum, N.,Wilson, I.A.,Law, M. (deposition date: 2017-11-08, release date: 2018-12-26, Last modification date: 2024-11-13)

Primary citation

Tzarum, N.,Giang, E.,Kong, L.,He, L.,Prentoe, J.,Augestad, E.,Hua, Y.,Castillo, S.,Lauer, G.M.,Bukh, J.,Zhu, J.,Wilson, I.A.,Law, M.
Genetic and structural insights into broad neutralization of hepatitis C virus by human VH1-69 antibodies.
Sci Adv, 5:eaav1882-eaav1882, 2019

PubMed Abstract: An effective vaccine to the antigenically diverse hepatitis C virus (HCV) must target conserved immune epitopes. Here, we investigate cross-neutralization of HCV genotypes by broadly neutralizing antibodies (bNAbs) encoded by the relatively abundant human gene family . We have deciphered the molecular requirements for cross-neutralization by this unique class of human antibodies from crystal structures of HCV E2 in complex with bNAbs. An unusually high binding affinity is found for germ line-reverted versions of V1-69 precursor antibodies, and neutralization breadth is acquired during affinity maturation. Deep sequencing analysis of an HCV-immune B cell repertoire further demonstrates the importance of the gene family in the generation of HCV bNAbs. This study therefore provides critical insights into immune recognition of HCV with important implications for rational vaccine design.

PubMed: 30613781
DOI: 10.1126/sciadv.aav1882

Experimental method

X-RAY DIFFRACTION (2.799 Å)