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Polysialic acid is a cellular receptor for human adenovirus 52

Lenman, Annasara; Liaci, A. Manuel; Liu, Yan; Frängsmyr, Lars; Frank, Martin; Blaum, Bärbel S.; Chai, Wengang; Podgorski, Iva I.; Harrach, Balázs; Benkő, Mária; Feizi, Ten; Stehle, Thilo; Arnberg, Niklas (2018) Polysialic acid is a cellular receptor for human adenovirus 52. Proceedings of the National Academy of Sciences, 115 (18). E4264-E4273. ISSN 0027-8424

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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.

Item Type: Article
Additional Information: The neoglycolipid-based glycan microarrays contain several saccharides provided by collaborators whom we thank as well as members of the Glycosciences Laboratory for their collaboration in the establishment of the microarray system. We gratefully acknowledge support from the Swiss Light Source staff during X-ray data collection. This investigation was supported by Swedish Cancer Society Grant CAN 2015/695, Cancer Research Foundation in Northern Sweden Grant AMP 16-794, Knut and Alice Wallenberg Foundation Grant KAW 2013.0019, German Research Foundation Grant DFG-SFB685, ViroCarb Grant FOR 2327, Marie Curie Initial Training Network "ADVance" Grant FP7-290002, the Glycobiology/Glycobiotechnology Program of the Baden-Wurttemberg Foundation, and Welcome Trust Grants WT093378MA/Z/10/Z/ and WT099197/Z/12/Z.
Uncontrolled Keywords: glycan microarray; glycan receptor; human adenovirus; polysialic acid; short fiber
Subjects: NATURAL SCIENCES > Biology > Microbiology
Divisions: Division of Molecular Medicine
Depositing User: Iva Škrinjar
Date Deposited: 19 Nov 2019 13:25
DOI: 10.1073/pnas.1716900115

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