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Crystallographic and glycan microarray analysis of human polyomavirus 9 VP1 identifies N-glycolyl neuraminic acid as a receptor candidate

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.1128/JVI.03455-13
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Affiliation
  1. National Research Council of Canada. Human Health Therapeutics
FormatText, Article
Subjectglycan; n glycoloylneuraminic acid; oligosaccharide; protein VP1; binding site; complex formation; cross reaction; crystal structure; crystallography; hydrogen bond; microarray analysis; molecular cloning; nucleotide sequence; Polyoma virus; Polyomavirus 9 VP1; protein expression; receptor binding; structure analysis; viral tropism; Capsid Proteins; Cloning, Molecular; Crystallography; Hydrogen Bonding; Microarray Analysis; Models, Molecular; Neuraminic Acids; Polyomavirus; Polysaccharides; Protein Conformation
Abstract
Human polyomavirus 9 (HPyV9) is a closely related homologue of simian B-lymphotropic polyomavirus (LPyV). In order to define the architecture and receptor binding properties of HPyV9, we solved high-resolution crystal structures of its major capsid protein, VP1, in complex with three putative oligosaccharide receptors identified by glycan microarray screening. Comparison of the properties of HPyV9 VP1 with the known structure and glycan-binding properties of LPyV VP1 revealed that both viruses engage short sialylated oligosaccharides, but small yet important differences in specificity were detected. Surprisingly, HPyV9 VP1 preferentially binds sialyllactosamine compounds terminating in 5-N-glycolyl neuraminic acid (Neu5Gc) over those terminating in 5-N-acetyl neuraminic acid (Neu5Ac), whereas LPyV does not exhibit such a preference. The structural analysis demonstrated that HPyV9 makes specific contacts, via hydrogen bonds, with the extra hydroxyl group present in Neu5Gc. An equivalent hydrogen bond cannot be formed by LPyV VP1. © 2014, American Society for Microbiology.
Publication date
In
  • Journal of Virology 88, no. 11 (2014): 6100–6111.
LanguageEnglish
Peer reviewedYes
NPARC number21272287
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Record identifier4286a9e8-83e1-404b-93d2-3b15daef621e
Record created2014-07-23
Record modified2020-04-22
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