Polysialic acid is a cellular receptor for human adenovirus 52 (CROSBI ID 250749)
Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija
Podaci o odgovornosti
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
engleski
Polysialic acid is a cellular receptor for human adenovirus 52
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.
human adenovirus ; short fiber ; polysialic acid ; glycan receptor ; glycan microarray
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Podaci o izdanju
115 (18)
2018.
E4264-E4273
objavljeno
0027-8424
1091-6490
10.1073/pnas.1716900115
Povezanost rada
Biologija