3NXD

JC polyomavirus VP1 in complex with LSTc

3NXD の概要

• エントリーDOI: 10.2210/pdb3nxd/pdb
• 関連するPDBエントリー: 1vps 3NXG 3bwr
• 分子名称: Major capsid protein VP1, N-acetyl-alpha-neuraminic acid-(2-6)-beta-D-galactopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-3)-beta-D-galactopyranose-(1-4)-beta-D-glucopyranose, GLYCEROL, ... (5 entities in total)
• 機能のキーワード: beta-sandwich with jelly roll topology, major capsid protein, viral protein
• 由来する生物種: JC polyomavirus (JCPyV)
• 細胞内の位置: Virion: P03089
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 153209.95

構造登録者

Neu, U.,Stroeh, L.J.,Stehle, T. (登録日: 2010-07-13, 公開日: 2010-11-17, 最終更新日: 2024-02-21)

主引用文献

Neu, U.,Maginnis, M.S.,Palma, A.S.,Stroh, L.J.,Nelson, C.D.,Feizi, T.,Atwood, W.J.,Stehle, T.
Structure-function analysis of the human JC polyomavirus establishes the LSTc pentasaccharide as a functional receptor motif.
Cell Host Microbe, 8:309-319, 2010

PubMed Abstract: The human JC polyomavirus (JCV) causes a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML), in immunocompromised individuals. Current treatment options for PML are inadequate. Sialylated oligosaccharides and the serotonin receptor are known to be necessary for JCV entry, but the molecular interactions underlying JCV attachment remain unknown. Using glycan array screening and viral infectivity assays, we identify a linear sialylated pentasaccharide with the sequence NeuNAc-α2,6-Gal-β1,4-GlcNAc-β1,3-Gal-β1,4-Glc (LSTc) present on host glycoproteins and glycolipids as a specific JCV recognition motif. The crystal structure of the JCV capsid protein VP1 was solved alone and in complex with LSTc. It reveals extensive interactions with the terminal sialic acid of the LSTc motif and specific recognition of an extended conformation of LSTc. Mutations in the JCV oligosaccharide-binding sites abolish cell attachment, viral spread, and infectivity, further validating the importance of this interaction. Our findings provide a powerful platform for the development of antiviral compounds.

PubMed: 20951965
DOI: 10.1016/j.chom.2010.09.004

実験手法

X-RAY DIFFRACTION (2 Å)