Polysialic acid is a cellular receptor for human adenovirus 52
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Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2018-05-01
Online Publication Date
2018-05-01
2018-06-15T11:27:12Z
Date Acceptance
2018-03-12
ISSN
0027-8424
Publisher
National Academy of Sciences
Start Page
E4264
End Page
E4273
Journal / Book Title
Proceedings of the National Academy of Sciences of the United States of America
Volume
115
Issue
18
Copyright Statement
Copyright © 2018 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Source Database
web-of-science
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000431119600017&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
human adenovirus
short fiber
polysialic acid
glycan receptor
glycan microarray
ADHESION MOLECULE
SIALIC-ACID
NERVOUS-SYSTEM
CRYSTAL-STRUCTURE
DENDRITIC CELLS
B ADENOVIRUSES
SENSORY AXONS
LUNG-CANCER
SPINAL-CORD
SYNCAM 1
MD Multidisciplinary
Publication Status
Published
Date Publish Online
2018-04-19