5NC1

Structure of the distal domain of mouse adenovirus 2 fibre bound to N-acetyl-glucosamine

Summary for 5NC1

• Entry DOI: 10.2210/pdb5nc1/pdb
• Related: 5N83 5N8D 5NBH
• Descriptor: Fiber, 2-acetamido-2-deoxy-beta-D-glucopyranose, SULFATE ION, ... (5 entities in total)
• Functional Keywords: triple beta-spiral, 3-bladed propeller, abcj-ghid topology, n-acetyl-glucosamine binding, viral protein
• Biological source: Murine adenovirus 2
• Total number of polymer chains: 3
• Total formula weight: 79245.18

Authors

Singh, A.K.,van Raaij, M.J. (deposition date: 2017-03-03, release date: 2018-03-14, Last modification date: 2024-01-17)

Primary citation

Singh, A.K.,Nguyen, T.H.,Vidovszky, M.Z.,Harrach, B.,Benko, M.,Kirwan, A.,Joshi, L.,Kilcoyne, M.,Berbis, M.A.,Canada, F.J.,Jimenez-Barbero, J.,Menendez, M.,Wilson, S.S.,Bromme, B.A.,Smith, J.G.,van Raaij, M.J.
Structure and N-acetylglucosamine binding of the distal domain of mouse adenovirus 2 fibre.
J. Gen. Virol., 99:1494-1508, 2018

PubMed 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.

PubMed: 30277856
DOI: 10.1099/jgv.0.001145

Experimental method

X-RAY DIFFRACTION (2 Å)