1. European Molecular Biology Laboratory, Grenoble Outstation, c/o Institut Laue Langevin, BP 156, 38042 Grenoble Cedex 9, France
2. Institut de Biologie Structurale (CEA-CNRS), 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France

Correspondence to: Stephen Cusack¹ Correspondence and requests for materials should be addressed to S.C. (e-mail: Email: cusack@embl-grenoble.fr). Atomic co-ordinates and structure factors are available from the Protein Data Bank under accession numbers 1QIU and R1QIUSF, respectively.

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 -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.