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A triple β-spiral in the adenovirus fibre shaft reveals a new structural motif for a fibrous protein

Nature volume 401, pages 935–938 (1999)Cite this article

Abstract

Human adenoviruses1 are responsible for respiratory, gastro-enteric and ocular infections2 and can serve as gene therapy vectors3. They form icosahedral particles with 240 copies of the trimeric hexon protein arranged on the planes and a penton complex at each of the twelve vertices. The penton consists of a pentameric base, implicated in virus internalization4, and a protruding trimeric fibre, responsible for receptor attachment5. The fibres are homo-trimeric proteins containing an amino-terminal penton base attachment domain, a long, thin central shaft and a carboxy-terminal cell attachment or head domain. The shaft domain contains a repeating sequence motif with an invariant glycine or proline and a conserved pattern of hydrophobic residues6. Here we describe the crystal structure at 2.4 Å resolution of a recombinant protein containing the four distal repeats of the adenovirus type 2 fibre shaft plus the receptor-binding head domain. The structure reveals a novel triple β-spiral fibrous fold for the shaft. Implications for folding of fibrous proteins (misfolding of shaft peptides leads to amyloid-like fibrils) and for the design of a new class of artificial, silk-like fibrous materials are discussed.

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Figure 1: The adenovirus fibre fold.
Figure 2: Alignment of the 22 repeats15 in the Ad2 shaft.
Figure 3: Interactions in the shaft.
Figure 4: Space-filled representation of a model containing 21 repeats of the shaft.

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Acknowledgements

We thank P. Goeltz and N. Cohet for help with cloning, expression and purification and J. Gagnon for comments. M.J.v.R. was supported by an EU Biotech II fellowship. The EMBL-ESRF Joint Structural Biology Group provided synchrotron radiation facilities.

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Authors and Affiliations

  1. European Molecular Biology Laboratory, Grenoble Outstation, c/o Institut Laue Langevin, BP 156, Grenoble, 38042, Cedex 9, France

    Mark J. van Raaij & Stephen Cusack

  2. Institut de Biologie Structurale (CEA-CNRS), 41 rue Jules Horowitz, Grenoble, 38027, Cedex 1, France

    Anna Mitraki & Gilles Lavigne

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  1. Mark J. van Raaij
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  4. Stephen Cusack
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Correspondence to Stephen Cusack.

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van Raaij, M., Mitraki, A., Lavigne, G. et al. A triple β-spiral in the adenovirus fibre shaft reveals a new structural motif for a fibrous protein. Nature 401, 935–938 (1999). https://doi.org/10.1038/44880

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