期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 18, 页码 E4264-E4273出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1716900115
关键词
human adenovirus; short fiber; polysialic acid; glycan receptor; glycan microarray
资金
- Swedish Cancer Society [CAN 2015/695]
- Cancer Research Foundation in Northern Sweden [AMP 16-794]
- Knut and Alice Wallenberg Foundation [KAW 2013.0019]
- German Research Foundation [DFG-SFB685]
- ViroCarb [FOR 2327]
- Marie Curie Initial Training Network ADVance Grant [FP7-290002]
- Glycobiology/Glycobiotechnology Program of the Baden-Wurttemberg Foundation
- Welcome Trust [WT093378MA/Z/10/Z/, WT099197/Z/12/Z]
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 alpha-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.
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