Structural polymorphism of the antigenic loop in HBV surface antigen dictates binding of diverse neutralizing antibodies
Abstract The Hepatitis B Virus (HBV) poses a significant health threat, causing millions of deaths each year. Hepatitis B surface antigen (HBsAg), the sole membrane protein on the HBV viral envelope, plays crucial roles in viral attachment to host cells and serves as the target for neutralizing anti...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Publishing Group
2025-06-01
|
| Series: | Cell Discovery |
| Online Access: | https://doi.org/10.1038/s41421-025-00803-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850207323693252608 |
|---|---|
| author | Xiao He Weiyu Tao Yunlu Kang Jiaxuan Xu Xiaoyu Liu Lei Chen |
| author_facet | Xiao He Weiyu Tao Yunlu Kang Jiaxuan Xu Xiaoyu Liu Lei Chen |
| author_sort | Xiao He |
| collection | DOAJ |
| description | Abstract The Hepatitis B Virus (HBV) poses a significant health threat, causing millions of deaths each year. Hepatitis B surface antigen (HBsAg), the sole membrane protein on the HBV viral envelope, plays crucial roles in viral attachment to host cells and serves as the target for neutralizing antibodies (NAbs). Despite its functional and therapeutic significance, the mechanisms by which NAbs recognize HBsAg remain elusive. Here, we found that HBsAg proteins exist in distinct subtypes and are recognized by different groups of antibodies. Cryo-electron microscopy (Cryo-EM) structures of HBsAg dimers in complex with NAb Fab fragments reveal that the antigenic loop (AGL) of these distinct HBsAg types share a common structural core comprised of four β-strands. However, their surface structures exhibit unexpected polymorphism due to distinct disulfide bond linkages within the AGL region. This structural polymorphism determines the recognition of HBsAg by different groups of NAbs. |
| format | Article |
| id | doaj-art-7450a6739abf41debf5da27642ae13a8 |
| institution | OA Journals |
| issn | 2056-5968 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Discovery |
| spelling | doaj-art-7450a6739abf41debf5da27642ae13a82025-08-20T02:10:34ZengNature Publishing GroupCell Discovery2056-59682025-06-011111910.1038/s41421-025-00803-2Structural polymorphism of the antigenic loop in HBV surface antigen dictates binding of diverse neutralizing antibodiesXiao He0Weiyu Tao1Yunlu Kang2Jiaxuan Xu3Xiaoyu Liu4Lei Chen5State Key Laboratory of Membrane Biology, College of Future Technology, Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking UniversityState Key Laboratory of Membrane Biology, College of Future Technology, Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking UniversityState Key Laboratory of Membrane Biology, College of Future Technology, Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking UniversityState Key Laboratory of Membrane Biology, College of Future Technology, Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking UniversityAcademy for Advanced Interdisciplinary Studies, Peking UniversityState Key Laboratory of Membrane Biology, College of Future Technology, Institute of Molecular Medicine, Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking UniversityAbstract The Hepatitis B Virus (HBV) poses a significant health threat, causing millions of deaths each year. Hepatitis B surface antigen (HBsAg), the sole membrane protein on the HBV viral envelope, plays crucial roles in viral attachment to host cells and serves as the target for neutralizing antibodies (NAbs). Despite its functional and therapeutic significance, the mechanisms by which NAbs recognize HBsAg remain elusive. Here, we found that HBsAg proteins exist in distinct subtypes and are recognized by different groups of antibodies. Cryo-electron microscopy (Cryo-EM) structures of HBsAg dimers in complex with NAb Fab fragments reveal that the antigenic loop (AGL) of these distinct HBsAg types share a common structural core comprised of four β-strands. However, their surface structures exhibit unexpected polymorphism due to distinct disulfide bond linkages within the AGL region. This structural polymorphism determines the recognition of HBsAg by different groups of NAbs.https://doi.org/10.1038/s41421-025-00803-2 |
| spellingShingle | Xiao He Weiyu Tao Yunlu Kang Jiaxuan Xu Xiaoyu Liu Lei Chen Structural polymorphism of the antigenic loop in HBV surface antigen dictates binding of diverse neutralizing antibodies Cell Discovery |
| title | Structural polymorphism of the antigenic loop in HBV surface antigen dictates binding of diverse neutralizing antibodies |
| title_full | Structural polymorphism of the antigenic loop in HBV surface antigen dictates binding of diverse neutralizing antibodies |
| title_fullStr | Structural polymorphism of the antigenic loop in HBV surface antigen dictates binding of diverse neutralizing antibodies |
| title_full_unstemmed | Structural polymorphism of the antigenic loop in HBV surface antigen dictates binding of diverse neutralizing antibodies |
| title_short | Structural polymorphism of the antigenic loop in HBV surface antigen dictates binding of diverse neutralizing antibodies |
| title_sort | structural polymorphism of the antigenic loop in hbv surface antigen dictates binding of diverse neutralizing antibodies |
| url | https://doi.org/10.1038/s41421-025-00803-2 |
| work_keys_str_mv | AT xiaohe structuralpolymorphismoftheantigenicloopinhbvsurfaceantigendictatesbindingofdiverseneutralizingantibodies AT weiyutao structuralpolymorphismoftheantigenicloopinhbvsurfaceantigendictatesbindingofdiverseneutralizingantibodies AT yunlukang structuralpolymorphismoftheantigenicloopinhbvsurfaceantigendictatesbindingofdiverseneutralizingantibodies AT jiaxuanxu structuralpolymorphismoftheantigenicloopinhbvsurfaceantigendictatesbindingofdiverseneutralizingantibodies AT xiaoyuliu structuralpolymorphismoftheantigenicloopinhbvsurfaceantigendictatesbindingofdiverseneutralizingantibodies AT leichen structuralpolymorphismoftheantigenicloopinhbvsurfaceantigendictatesbindingofdiverseneutralizingantibodies |