{"title":"乙型肝炎病毒表面抗原抗原环的对称结构。","authors":"Weiyu Tao, Xiao He, Lei Chen","doi":"10.1016/j.jmb.2025.169483","DOIUrl":null,"url":null,"abstract":"<p><p>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 AGL<sub>Type B</sub> and its symmetry remain elusive. Here, we present the cryo-EM structure of AGL<sub>Type B</sub> in complex with the Fab fragment of the NAb H020. The complete structure of AGL<sub>Type B</sub> reveals its two-fold symmetry and it can bind two Fab<sub>H020</sub> fragments. Further analysis elucidates the underlying mechanism of pan-serotype neutralizing capability of H020 and how escape mutations hinder its binding.</p>","PeriodicalId":369,"journal":{"name":"Journal of Molecular Biology","volume":" ","pages":"169483"},"PeriodicalIF":4.5000,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The symmetric structure of the antigenic loop in Type B HBV surface antigen.\",\"authors\":\"Weiyu Tao, Xiao He, Lei Chen\",\"doi\":\"10.1016/j.jmb.2025.169483\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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 AGL<sub>Type B</sub> and its symmetry remain elusive. Here, we present the cryo-EM structure of AGL<sub>Type B</sub> in complex with the Fab fragment of the NAb H020. The complete structure of AGL<sub>Type B</sub> reveals its two-fold symmetry and it can bind two Fab<sub>H020</sub> fragments. Further analysis elucidates the underlying mechanism of pan-serotype neutralizing capability of H020 and how escape mutations hinder its binding.</p>\",\"PeriodicalId\":369,\"journal\":{\"name\":\"Journal of Molecular Biology\",\"volume\":\" \",\"pages\":\"169483\"},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2025-10-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Molecular Biology\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jmb.2025.169483\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Molecular Biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.jmb.2025.169483","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
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. Further analysis elucidates the underlying mechanism of pan-serotype neutralizing capability of H020 and how escape mutations hinder its binding.
期刊介绍：
Journal of Molecular Biology (JMB) provides high quality, comprehensive and broad coverage in all areas of molecular biology. The journal publishes original scientific research papers that provide mechanistic and functional insights and report a significant advance to the field. The journal encourages the submission of multidisciplinary studies that use complementary experimental and computational approaches to address challenging biological questions.
Research areas include but are not limited to: Biomolecular interactions, signaling networks, systems biology; Cell cycle, cell growth, cell differentiation; Cell death, autophagy; Cell signaling and regulation; Chemical biology; Computational biology, in combination with experimental studies; DNA replication, repair, and recombination; Development, regenerative biology, mechanistic and functional studies of stem cells; Epigenetics, chromatin structure and function; Gene expression; Membrane processes, cell surface proteins and cell-cell interactions; Methodological advances, both experimental and theoretical, including databases; Microbiology, virology, and interactions with the host or environment; Microbiota mechanistic and functional studies; Nuclear organization; Post-translational modifications, proteomics; Processing and function of biologically important macromolecules and complexes; Molecular basis of disease; RNA processing, structure and functions of non-coding RNAs, transcription; Sorting, spatiotemporal organization, trafficking; Structural biology; Synthetic biology; Translation, protein folding, chaperones, protein degradation and quality control.
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