Polysialic acid is a cellular receptor for human adenovirus 52.

Autor:	Lenman A; Division of Virology, Department of Clinical Microbiology, and Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden; annasara.lenman@umu.se thilo.stehle@uni-tuebingen.de., Liaci AM; Interfaculty Institute of Biochemistry, University of Tübingen, D-72076 Tübingen, Germany., Liu Y; Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom., Frängsmyr L; Division of Virology, Department of Clinical Microbiology, and Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden., Frank M; Biognos AB, SE-40274 Gothenburg, Sweden., Blaum BS; Interfaculty Institute of Biochemistry, University of Tübingen, D-72076 Tübingen, Germany., Chai W; Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom., Podgorski II; Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, H-1143 Budapest, Hungary.; Division of Molecular Medicine, Rudjer Boskovic Institute, 10000 Zagreb, Croatia., Harrach B; Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, H-1143 Budapest, Hungary., Benkő M; Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, H-1143 Budapest, Hungary., Feizi T; Glycosciences Laboratory, Department of Medicine, Imperial College London, W12 0NN London, United Kingdom., Stehle T; Interfaculty Institute of Biochemistry, University of Tübingen, D-72076 Tübingen, Germany; annasara.lenman@umu.se thilo.stehle@uni-tuebingen.de.; Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN 37232., Arnberg N; Division of Virology, Department of Clinical Microbiology, and Laboratory for Molecular Infection Medicine Sweden, Umeå University, SE-90185 Umeå, Sweden.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2018 May 01; Vol. 115 (18), pp. E4264-E4273. Date of Electronic Publication: 2018 Apr 19.
DOI:	10.1073/pnas.1716900115
Abstrakt:	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 . Competing Interests: The authors declare no conflict of interest. (Copyright © 2018 the Author(s). Published by PNAS.)
Databáze:	MEDLINE
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