Polysialic acid is a cellular receptor for human adenovirus 52.
Annasara LenmanA Manuel LiaciYan LiuLars FrängsmyrMartin FrankBärbel S BlaumWengang ChaiIva I PodgorskiBalázs HarrachMária BenkőTen FeiziThilo StehleNiklas ArnbergPublished in: Proceedings of the National Academy of Sciences of the United States of America (2018)
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.
Keyphrases
- endothelial cells
- molecular dynamics simulations
- pluripotent stem cells
- high resolution
- binding protein
- induced apoptosis
- magnetic resonance
- sars cov
- molecular docking
- magnetic resonance imaging
- signaling pathway
- small molecule
- cell death
- gene therapy
- cell surface
- genome wide
- candida albicans
- subarachnoid hemorrhage