4X17

JC Mad-1 polyomavirus VP1 in complex with GD1b oligosaccharide

Summary for 4X17

• Entry DOI: 10.2210/pdb4x17/pdb
• Related: 3NXD 3NXG
• Descriptor: Major capsid protein VP1, N-acetyl-alpha-neuraminic acid-(2-8)-N-acetyl-alpha-neuraminic acid, GLYCEROL, ... (7 entities in total)
• Functional Keywords: beta-sandwich, jelly-roll, viral major capsid protein, glycan, viral protein
• Biological source: JC polyomavirus (JCPyV)
• Cellular location: Virion: P03089
• Total number of polymer chains: 5
• Total formula weight: 153967.89

Authors

Stroh, L.J.,Stehle, T. (deposition date: 2014-11-24, release date: 2015-04-22, Last modification date: 2024-01-10)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.75 Å)