Polysialic acid is a cellular receptor for human adenovirus 52

Annasara Lenman, A. Manuel Liaci, Yan Liu, Lars Frängsmyr, Martin Frank, Bärbel S. Blaum, Wengang Chai, Iva I. Podgorski, Balázs Harrach, Mária Benko, Ten Feizi, Thilo Stehle, Niklas Arnberg

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26 Citations (Scopus)


Human adenovirus 52 (HAdV-52) is one of only three known HAdVs equipped with both a long and a short fiber protein. While the long fiber binds to the coxsackie and adenovirus receptor, the function of the short fiber in the virus life cycle is poorly understood. Here, we show, by glycan microarray analysis and cellular studies, that the short fiber knob (SFK) of HAdV-52 recognizes long chains of α-2,8-linked polysialic acid (polySia), a large posttranslational modification of selected carrier proteins, and that HAdV-52 can use polySia as a receptor on target cells. X-ray crystallography, NMR, molecular dynamics simulation, and structure-guided mutagenesis of the SFK reveal that the nonreducing, terminal sialic acid of polySia engages the protein with direct contacts, and that specificity for polySia is achieved through subtle, transient electrostatic interactions with additional sialic acid residues. In this study, we present a previously unrecognized role for polySia as a cellular receptor for a human viral pathogen. Our detailed analysis of the determinants of specificity for this interaction has general implications for protein–carbohydrate interactions, particularly concerning highly charged glycan structures, and provides interesting dimensions on the biology and evolution of members of Human mastadenovirus G.

Original languageEnglish
Pages (from-to)E4264-E42736
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number18
Publication statusPublished - May 1 2018


  • Glycan microarray
  • Glycan receptor
  • Human adenovirus
  • Polysialic acid
  • Short fiber

ASJC Scopus subject areas

  • General

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    Lenman, A., Manuel Liaci, A., Liu, Y., Frängsmyr, L., Frank, M., Blaum, B. S., Chai, W., Podgorski, I. I., Harrach, B., Benko, M., Feizi, T., Stehle, T., & Arnberg, N. (2018). Polysialic acid is a cellular receptor for human adenovirus 52. Proceedings of the National Academy of Sciences of the United States of America, 115(18), E4264-E42736. https://doi.org/10.1073/pnas.1716900115