The Symmetric Structure of the Antigenic Loop in Type B HBV Surface Antigen.

Hepatitis B virus (HBV) is an enveloped virus with HBV surface antigen (HBsAg) as the only protein on its viral membrane. The extracellular antigenic loop (AGL) of HBsAg plays a crucial role in viral attachment to host cells, serves as the primary target for neutralizing antibodies (NAbs), and is subject to escape mutations. Previous studies have shown that the AGL exhibits two different structures (Type A and Type B) dictated by distinct disulfide bond linkage. However, due to the flexibility of some regions in previous structure, the complete model of AGLType B and its symmetry remain elusive. Here, we present the cryo-EM structure of AGLType B in complex with the Fab fragment of the NAb H020. The complete structure of AGLType B reveals its two-fold symmetry and it can bind two FabH020 fragments simultaneously. Further analysis elucidates the underlying mechanism of pan-serotype neutralizing capability of H020 and how escape mutations hinder its binding.