6MEG

Crystal structure of human monoclonal antibody HEPC46

Summary for 6MEG

• Entry DOI: 10.2210/pdb6meg/pdb
• Descriptor: antibody HEPC46 Heavy Chain, antibody HEPC46 Light Chain (3 entities in total)
• Functional Keywords: hcv glycoprotein, broadly neutralizing antibodies, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 47619.81

Authors

Flyak, A.I.,Bjorkman, P.J. (deposition date: 2018-09-06, release date: 2018-11-21, Last modification date: 2024-11-13)

Primary citation

Flyak, A.I.,Ruiz, S.,Colbert, M.D.,Luong, T.,Crowe Jr., J.E.,Bailey, J.R.,Bjorkman, P.J.
HCV Broadly Neutralizing Antibodies Use a CDRH3 Disulfide Motif to Recognize an E2 Glycoprotein Site that Can Be Targeted for Vaccine Design.
Cell Host Microbe, 24:703-716.e3, 2018

PubMed Abstract: Hepatitis C virus (HCV) vaccine efforts are hampered by the extensive genetic diversity of HCV envelope glycoproteins E1 and E2. Structures of broadly neutralizing antibodies (bNAbs) (e.g., HEPC3, HEPC74) isolated from individuals who spontaneously cleared HCV infection facilitate immunogen design to elicit antibodies against multiple HCV variants. However, challenges in expressing HCV glycoproteins previously limited bNAb-HCV structures to complexes with truncated E2 cores. Here we describe crystal structures of full-length E2 ectodomain complexes with HEPC3 and HEPC74, revealing lock-and-key antibody-antigen interactions, E2 regions (including a target of immunogen design) that were truncated or disordered in E2 cores, and an antibody CDRH3 disulfide motif that exhibits common interactions with a conserved epitope despite different bNAb-E2 binding orientations. The structures display unusual features relevant to common genetic signatures of HCV bNAbs and demonstrate extraordinary plasticity in antibody-antigen interactions. In addition, E2 variants that bind HEPC3/HEPC74-like germline precursors may represent candidate vaccine immunogens.

PubMed: 30439340
DOI: 10.1016/j.chom.2018.10.009

Experimental method

X-RAY DIFFRACTION (1.41 Å)