Cryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1
Abstract Sudan ebolavirus (SUDV), like Ebola ebolavirus (EBOV), poses a significant threat to global health and security due to its high lethality. However, unlike EBOV, there are no approved vaccines or treatments for SUDV, and its structural interaction with the endosomal receptor NPC1 remains unc...
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| Format: | Article |
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Nature Portfolio
2025-02-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07613-y |
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| author | Fan Bu Gang Ye Hailey Turner-Hubbard Morgan Herbst Bin Liu Fang Li |
| author_facet | Fan Bu Gang Ye Hailey Turner-Hubbard Morgan Herbst Bin Liu Fang Li |
| author_sort | Fan Bu |
| collection | DOAJ |
| description | Abstract Sudan ebolavirus (SUDV), like Ebola ebolavirus (EBOV), poses a significant threat to global health and security due to its high lethality. However, unlike EBOV, there are no approved vaccines or treatments for SUDV, and its structural interaction with the endosomal receptor NPC1 remains unclear. This study compares the glycoproteins of SUDV and EBOV (in their proteolytically primed forms) and their binding to human NPC1 (hNPC1). The findings reveal that the SUDV glycoprotein binds significantly more strongly to hNPC1 than the EBOV glycoprotein. Using cryo-EM, we determined the structure of the SUDV glycoprotein/hNPC1 complex, identifying four key residues in the SUDV glycoprotein that differ from those in the EBOV glycoprotein and influence hNPC1 binding: Ile79, Ala141, and Pro148 enhance binding, while Gln142 reduces it. Collectively, these residue differences account for SUDV’s stronger binding affinity for hNPC1. This study provides critical insights into receptor recognition across all viruses in the ebolavirus genus, including their interactions with receptors in bats, their suspected reservoir hosts. These findings advance our understanding of ebolavirus cell entry, tissue tropism, and host range. |
| format | Article |
| id | doaj-art-d64f5ba34f1c43d0a4330efc754643c2 |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-d64f5ba34f1c43d0a4330efc754643c22025-02-02T12:37:10ZengNature PortfolioCommunications Biology2399-36422025-02-01811810.1038/s42003-025-07613-yCryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1Fan Bu0Gang Ye1Hailey Turner-Hubbard2Morgan Herbst3Bin Liu4Fang Li5Department of Pharmacology, University of Minnesota Medical SchoolDepartment of Pharmacology, University of Minnesota Medical SchoolDepartment of Pharmacology, University of Minnesota Medical SchoolDepartment of Pharmacology, University of Minnesota Medical SchoolHormel Institute, University of MinnesotaDepartment of Pharmacology, University of Minnesota Medical SchoolAbstract Sudan ebolavirus (SUDV), like Ebola ebolavirus (EBOV), poses a significant threat to global health and security due to its high lethality. However, unlike EBOV, there are no approved vaccines or treatments for SUDV, and its structural interaction with the endosomal receptor NPC1 remains unclear. This study compares the glycoproteins of SUDV and EBOV (in their proteolytically primed forms) and their binding to human NPC1 (hNPC1). The findings reveal that the SUDV glycoprotein binds significantly more strongly to hNPC1 than the EBOV glycoprotein. Using cryo-EM, we determined the structure of the SUDV glycoprotein/hNPC1 complex, identifying four key residues in the SUDV glycoprotein that differ from those in the EBOV glycoprotein and influence hNPC1 binding: Ile79, Ala141, and Pro148 enhance binding, while Gln142 reduces it. Collectively, these residue differences account for SUDV’s stronger binding affinity for hNPC1. This study provides critical insights into receptor recognition across all viruses in the ebolavirus genus, including their interactions with receptors in bats, their suspected reservoir hosts. These findings advance our understanding of ebolavirus cell entry, tissue tropism, and host range.https://doi.org/10.1038/s42003-025-07613-y |
| spellingShingle | Fan Bu Gang Ye Hailey Turner-Hubbard Morgan Herbst Bin Liu Fang Li Cryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1 Communications Biology |
| title | Cryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1 |
| title_full | Cryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1 |
| title_fullStr | Cryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1 |
| title_full_unstemmed | Cryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1 |
| title_short | Cryo-EM structure of Sudan ebolavirus glycoprotein complexed with its human endosomal receptor NPC1 |
| title_sort | cryo em structure of sudan ebolavirus glycoprotein complexed with its human endosomal receptor npc1 |
| url | https://doi.org/10.1038/s42003-025-07613-y |
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