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J Gen Virol. 2018 Nov;99(11):1494-1508. doi: 10.1099/jgv.0.001145. Epub 2018 Oct 2.

Structure and N-acetylglucosamine binding of the distal domain of mouse adenovirus 2 fibre.

Author information

1
1​Departamento de Estructura de Macromoléculas, Centro Nacional de Biotecnologia (CNB-CSIC), Calle Darwin 3, 28049 Madrid, Spain.
2
†​Present address: School of Biosciences, Stacey Building, University of Kent, Canterbury CT2 7NJ, UK.
3
‡​Present address: Genetic Engineering Laboratory, Institute of Biotechnology (IBT-VAST), 18 Hoang Quoc Viet, Cau Giay, Hanoi, Vietnam.
4
2​Institute for Veterinary Medical Research, Centre for Agricultural Research, Hungarian Academy of Sciences, Budapest, Hungary.
5
3​Glycoscience Group, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland.
6
4​Carbohydrate Signalling Group, Microbiology, School of Natural Sciences, National University of Ireland, Galway, Ireland.
7
5​Departamento de Biología Estructural y Química, Centro de Investigaciones Biológicas (CIB-CSIC), Madrid, Spain.
8
§​Present address: Molecular Recognition and Host-Pathogen Interactions Unit, CIC bioGUNE, Bizkaia Technology Park, Building 801A, 48170 Derio, Spain.
9
¶​Present address: Ikerbasque, Basque Foundation for Science, Maria Diaz de Haro 13, 48009 Bilbao, Spain.
10
6​Departamento de Química Física-Biológica, Instituto de Química Física Rocasolano (IQFR-CSIC), Madrid, Spain.
11
7​CIBER of Respiratory Diseases (CIBERES-ISCIII), Madrid, Spain.
12
8​Department of Microbiology, University of Washington, Seattle, WA, USA.

Abstract

Murine adenovirus 2 (MAdV-2) infects cells of the mouse gastrointestinal tract. Like human adenoviruses, it is a member of the genus Mastadenovirus, family Adenoviridae. The MAdV-2 genome has a single fibre gene that expresses a 787 residue-long protein. Through analogy to other adenovirus fibre proteins, it is expected that the carboxy-terminal virus-distal head domain of the fibre is responsible for binding to the host cell, although the natural receptor is unknown. The putative head domain has little sequence identity to adenovirus fibres of known structure. In this report, we present high-resolution crystal structures of the carboxy-terminal part of the MAdV-2 fibre. The structures reveal a domain with the typical adenovirus fibre head topology and a domain containing two triple β-spiral repeats of the shaft domain. Through glycan microarray profiling, saturation transfer difference nuclear magnetic resonance spectroscopy, isothermal titration calorimetry and site-directed mutagenesis, we show that the fibre specifically binds to the monosaccharide N-acetylglucosamine (GlcNAc). The crystal structure of the complex reveals that GlcNAc binds between the AB and CD loops at the top of each of the three monomers of the MAdV-2 fibre head. However, infection competition assays show that soluble GlcNAc monosaccharide and natural GlcNAc-containing polymers do not inhibit infection by MAdV-2. Furthermore, site-directed mutation of the GlcNAc-binding residues does not prevent the inhibition of infection by soluble fibre protein. On the other hand, we show that the MAdV-2 fibre protein binds GlcNAc-containing mucin glycans, which suggests that the MAdV-2 fibre protein may play a role in viral mucin penetration in the mouse gut.

KEYWORDS:

adenovirus fibre; affinity; crystal structure; gastrointestinal tract; infection inhibition; ligand

PMID:
30277856
DOI:
10.1099/jgv.0.001145

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