AI Article Synopsis
- Dengue NS1 plays a crucial role in dengue hemorrhagic fever (DHF) and exists in multiple forms, including intracellular dimeric (iNS1) and extracellular secreted (sNS1) configurations.
- Previous research indicated that sNS1 predominantly forms hexamers, but this study utilized cryo-electron microscopy (cryoEM) to reveal that sNS1 also consists of stable and loose tetramers.
- The conformation of the N-terminal domain affects the stability of these tetramers, and the findings can aid in developing new therapies for dengue by detailing the organization of sNS1's oligomeric states.
Article Abstract
Dengue virus infection can cause dengue hemorrhagic fever (DHF). Dengue NS1 is multifunctional. The intracellular dimeric NS1 (iNS1) forms part of the viral replication complex. Previous studies suggest the extracellular secreted NS1 (sNS1), which is a major factor contributing to DHF, exists as hexamers. The structure of the iNS1 is well-characterised but not that of sNS1. Here we show by cryoEM that the recombinant sNS1 exists in multiple oligomeric states: the tetrameric (stable and loose conformation) and hexameric structures. Stability of the stable and loose tetramers is determined by the conformation of their N-terminal domain - elongated β-sheet or β-roll. Binding of an anti-NS1 Fab breaks the loose tetrameric and hexameric sNS1 into dimers, whereas the stable tetramer remains largely unbound. Our results show detailed quaternary organization of different oligomeric states of sNS1 and will contribute towards the design of dengue therapeutics.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9643530 | PMC |
| http://dx.doi.org/10.1038/s41467-022-34415-1 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!