Polysialic acid is a cellular receptor for human adenovirus 52

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 115; no. 18; pp. E4264 - E4273
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 01.05.2018
• Series: PNAS Plus
• Subjects: Adenoviruses; Biological evolution; Biological Sciences; Carbohydrates; Crystallography; Electrostatic properties; Glycan; glycan microarray; glycan receptor; human adenovirus; Life cycle analysis; Life cycle engineering; Life cycles; Long fibers; Molecular dynamics; Molecular structure; Mutagenesis; NMR; Nuclear magnetic resonance; Pathogens; PNAS Plus; Polysialic acid; Proteins; short fiber; Short fibers; Studies; T cell receptors; Viruses; X-ray crystallography; polysialic acid; short fiber; human adenovirus; glycan microarray; glycan receptor
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1716900115

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.