Structures of two lyssavirus glycoproteins trapped in pre- and post-fusion states and the implications on the spatial-temporal conformational transition along with pH-decrease.
Lyssavirus glycoprotein plays a crucial role in mediating virus entry and serves as the major target for neutralizing antibodies. During membrane fusion, the lyssavirus glycoprotein undergoes a series of low-pH-induced conformational transitions. Here, we report the structures of Ikoma lyssavirus an...
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| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2025-02-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1012923 |
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| _version_ | 1850143467620007936 |
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| author | Fanli Yang Sheng Lin Xin Yuan Siqi Shu Yueru Yu Jing Yang Fei Ye Zimin Chen Bin He Jian Li Qi Zhao Haoyu Ye Yu Cao Guangwen Lu |
| author_facet | Fanli Yang Sheng Lin Xin Yuan Siqi Shu Yueru Yu Jing Yang Fei Ye Zimin Chen Bin He Jian Li Qi Zhao Haoyu Ye Yu Cao Guangwen Lu |
| author_sort | Fanli Yang |
| collection | DOAJ |
| description | Lyssavirus glycoprotein plays a crucial role in mediating virus entry and serves as the major target for neutralizing antibodies. During membrane fusion, the lyssavirus glycoprotein undergoes a series of low-pH-induced conformational transitions. Here, we report the structures of Ikoma lyssavirus and Mokola lyssavirus glycoproteins, with which we believe that we have trapped the proteins in pre-fusion and post-fusion states respectively. By analyzing the available lyssaviral glycoprotein structures, we present a sequential conformation-transition model, in which two structural elements in the glycoprotein undergo fine-modulated secondary structural transitions, changing the glycoprotein from a bended hairpin conformation to an extended linear conformation. In addition, such conformational change is further facilitated, as observed in our surface plasmon resonance assay, by the pH-regulated interactions between the membrane-proximal region and the pleckstrin homology and the fusion domains. The structural features elucidated in this study will facilitate the design of vaccines and anti-viral drugs against lyssaviruses. |
| format | Article |
| id | doaj-art-a5b6bb65ca3744f6bc20a0b266f3e3f0 |
| institution | OA Journals |
| issn | 1553-7366 1553-7374 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj-art-a5b6bb65ca3744f6bc20a0b266f3e3f02025-08-20T02:28:41ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742025-02-01212e101292310.1371/journal.ppat.1012923Structures of two lyssavirus glycoproteins trapped in pre- and post-fusion states and the implications on the spatial-temporal conformational transition along with pH-decrease.Fanli YangSheng LinXin YuanSiqi ShuYueru YuJing YangFei YeZimin ChenBin HeJian LiQi ZhaoHaoyu YeYu CaoGuangwen LuLyssavirus glycoprotein plays a crucial role in mediating virus entry and serves as the major target for neutralizing antibodies. During membrane fusion, the lyssavirus glycoprotein undergoes a series of low-pH-induced conformational transitions. Here, we report the structures of Ikoma lyssavirus and Mokola lyssavirus glycoproteins, with which we believe that we have trapped the proteins in pre-fusion and post-fusion states respectively. By analyzing the available lyssaviral glycoprotein structures, we present a sequential conformation-transition model, in which two structural elements in the glycoprotein undergo fine-modulated secondary structural transitions, changing the glycoprotein from a bended hairpin conformation to an extended linear conformation. In addition, such conformational change is further facilitated, as observed in our surface plasmon resonance assay, by the pH-regulated interactions between the membrane-proximal region and the pleckstrin homology and the fusion domains. The structural features elucidated in this study will facilitate the design of vaccines and anti-viral drugs against lyssaviruses.https://doi.org/10.1371/journal.ppat.1012923 |
| spellingShingle | Fanli Yang Sheng Lin Xin Yuan Siqi Shu Yueru Yu Jing Yang Fei Ye Zimin Chen Bin He Jian Li Qi Zhao Haoyu Ye Yu Cao Guangwen Lu Structures of two lyssavirus glycoproteins trapped in pre- and post-fusion states and the implications on the spatial-temporal conformational transition along with pH-decrease. PLoS Pathogens |
| title | Structures of two lyssavirus glycoproteins trapped in pre- and post-fusion states and the implications on the spatial-temporal conformational transition along with pH-decrease. |
| title_full | Structures of two lyssavirus glycoproteins trapped in pre- and post-fusion states and the implications on the spatial-temporal conformational transition along with pH-decrease. |
| title_fullStr | Structures of two lyssavirus glycoproteins trapped in pre- and post-fusion states and the implications on the spatial-temporal conformational transition along with pH-decrease. |
| title_full_unstemmed | Structures of two lyssavirus glycoproteins trapped in pre- and post-fusion states and the implications on the spatial-temporal conformational transition along with pH-decrease. |
| title_short | Structures of two lyssavirus glycoproteins trapped in pre- and post-fusion states and the implications on the spatial-temporal conformational transition along with pH-decrease. |
| title_sort | structures of two lyssavirus glycoproteins trapped in pre and post fusion states and the implications on the spatial temporal conformational transition along with ph decrease |
| url | https://doi.org/10.1371/journal.ppat.1012923 |
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