8PHZ

Helical reconstruction of CHIKV nsP3 helical scaffolds

8PHZ の概要

• エントリーDOI: 10.2210/pdb8phz/pdb
• EMDBエントリー: 17678
• 分子名称: Non-structural protein 3, ZINC ION (2 entities in total)
• 機能のキーワード: helical scaffold, replication complex, alpha granules, viral factories, viral protein
• 由来する生物種: Chikungunya virus strain S27-African prototype
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 287418.08

構造登録者

Reguera, J.,Hons, M.,Zimberger, C.,Ptchelkine, D.,Jones, R.,Desfosses, A. (登録日: 2023-06-20, 公開日: 2024-08-14, 最終更新日: 2025-01-22)

主引用文献

Kril, V.,Hons, M.,Amadori, C.,Zimberger, C.,Couture, L.,Bouery, Y.,Burlaud-Gaillard, J.,Karpov, A.,Ptchelkine, D.,Thienel, A.L.,Kummerer, B.M.,Desfosses, A.,Jones, R.,Roingeard, P.,Meertens, L.,Amara, A.,Reguera, J.
Alphavirus nsP3 organizes into tubular scaffolds essential for infection and the cytoplasmic granule architecture.
Nat Commun, 15:8106-8106, 2024

PubMed Abstract: Alphaviruses, such as chikungunya virus (CHIKV), are mosquito-borne viruses that represent a significant threat to human health due to the current context of global warming. Efficient alphavirus infection relies on the activity of the non-structural protein 3 (nsP3), a puzzling multifunctional molecule whose role in infection remains largely unknown. NsP3 is a component of the plasma membrane-bound viral RNA replication complex (vRC) essential for RNA amplification and is also found in large cytoplasmic aggregates of unknown function Here, we report the cryo-electron microscopy (cryo-EM) structure of the CHIKV nsP3 at 2.35 Å resolution. We show that nsP3 assembles into tubular structures made by a helical arrangement of its alphavirus unique domain (AUD). The nsP3 helical scaffolds are consistent with crown structures found on tomographic reconstructions of the mature viral RCs. In addition, nsP3 helices assemble into cytoplasmic granules organized in a network of tubular structures that contain viral genomic RNA and capsid as well as host factors required for productive infection. Structure-guided mutagenesis identified residues that prevent or disturb nsP3 assemblies, resulting in impaired viral replication or transcription. Altogether, our results reveal an unexpected nsP3-dependent molecular organization essential for different phases of alphavirus infection.

PubMed: 39285216
DOI: 10.1038/s41467-024-51952-z

実験手法

ELECTRON MICROSCOPY (2.35 Å)