4X0Y

JC polyomavirus VP1 from a genotype 3 strain

4X0Y の概要

• エントリーDOI: 10.2210/pdb4x0y/pdb
• 関連するPDBエントリー: 3NXD 3NXG
• 分子名称: Major capsid protein, GLYCEROL, 1,2-ETHANEDIOL, ... (5 entities in total)
• 機能のキーワード: beta-sandwich, jelly-roll, viral capsid protein, viral protein
• 由来する生物種: JC polyomavirus type 3 (JCPyV)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 152004.23

構造登録者

Stroh, L.J.,Stehle, T. (登録日: 2014-11-24, 公開日: 2015-04-22, 最終更新日: 2024-01-10)

主引用文献

Stroh, L.J.,Maginnis, M.S.,Blaum, B.S.,Nelson, C.D.,Neu, U.,Gee, G.V.,O'Hara, B.A.,Motamedi, N.,DiMaio, D.,Atwood, W.J.,Stehle, T.
The Greater Affinity of JC Polyomavirus Capsid for alpha 2,6-Linked Lactoseries Tetrasaccharide c than for Other Sialylated Glycans Is a Major Determinant of Infectivity.
J.Virol., 89:6364-6375, 2015

PubMed Abstract: The human JC polyomavirus (JCPyV) establishes an asymptomatic, persistent infection in the kidneys of the majority of the population and is the causative agent of the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) in immunosuppressed individuals. The Mad-1 strain of JCPyV, a brain isolate, was shown earlier to require α2,6-linked sialic acid on the lactoseries tetrasaccharide c (LSTc) glycan for attachment to host cells. In contrast, a JCPyV kidney isolate type 3 strain, WT3, has been reported to interact with sialic acid-containing gangliosides, but the role of these glycans in JCPyV infection has remained unclear. To help rationalize these findings and probe the effects of strain-specific differences on receptor binding, we performed a comprehensive analysis of the glycan receptor specificities of these two representative JCPyV strains using high-resolution X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, and correlated these data with the results of infectivity assays. We show here that capsid proteins of Mad-1 and WT3 JCPyV can both engage LSTc as well as multiple sialylated gangliosides. However, the binding affinities exhibit subtle differences, with the highest affinity observed for LSTc. Engagement of LSTc is a prerequisite for functional receptor engagement, while the more weakly binding gangliosides are not required for productive infection. Our findings highlight the complexity of virus-carbohydrate interactions and demonstrate that subtle differences in binding affinities, rather than the binding event alone, help determine tissue tropism and viral pathogenesis.

PubMed: 25855729
DOI: 10.1128/JVI.00489-15

実験手法

X-RAY DIFFRACTION (1.7 Å)