Structure, Folding and Assembly of Adenovirus Fibers

Abstract

Adenovirus fibers are trimeric proteins that protrude from the 12 five-fold vertices of the virion. They consist of three segments: a N-terminal tail, a thin shaft carrying 15-amino acid pseudo-repeats, and a C-terminal globular head (or knob) which recognizes theprimary cell receptor. Our recent folding studies have demonstrated that the fiber unfolds in SDS through a stable intermediate in which the C-terminal head and five repeats of the shaft remain folded and trimeric. This stable domain has been cloned and expressed in Escherichia coli and its structure has been solved at 2.4Å resolution. The structure reveals a novel triple β-spiral fibrous fold for the shaft. In order to assemble into the correct triple β-spiral conformation, the shaft needs to be brought into the correct registration. The globular head appears to act as the registration signal, and in its absence synthetic peptides corresponding to shaft sequences fail to assemble correctly. Instead, they aggregate and form amyloid-like fibrils. In this chapter we discuss the fiber as a model system to address the interplay between folding, assembly and misassembly of β-sheet proteins. We also discuss potential implications for materials science since this protein has been used as a model for synthetic fiber design.