Review
The ankyrin repeat: a diversity of interactions on a common structural framework

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Abstract

The ankyrin repeat is one of the most common protein sequence motifs. Recent X-ray and NMR structures of ankyrin-repeat proteins and their complexes have provided invaluable insights into the molecular basis of the extraordinary variety of biological activities of these molecules. In particular, they have begun to reveal how a large family of structurally related proteins can interact specifically with such a diverse array of macromolecular targets.

Section snippets

Structural organization of ANK repeats

The first three-dimensional structure of an ANK-repeat molecule, that of 53BP2 bound to the p53 cell-cycle tumour suppressor6, was determined almost ten years after the discovery of the motif. This and subsequent structures have shown that the ANK repeat consists of pairs of antiparallel α-helices stacked side by side and connected by a series of intervening β-hairpin motifs (Fig. 1a). The extended β-sheet projects away from the helical pairs almost at right angles to them, resulting in a

Intermolecular interactions

Eight X-ray structures of complexes involving ANK repeats have been determined (Table 1). Despite the overall sequence similarity shared by ANK proteins, the mechanism of binding to specific partner molecules varies considerably. Binding can use much of the available solvent-accessible surface, and contacts are not restricted to any particular secondary structural element within the ANK repeat. Nevertheless, these structures have revealed some common features of molecular interactions. The

Intramolecular interactions

The structure of a central 36-kDa fragment of Swi6 provides the only example so far of intramolecular interactions involving ANK repeats18 (Fig. 2d). In this case, a region that is capable of transcriptional activation in vivo23 interacts with a core domain consisting of five ANK-repeat motifs. The interaction surface on the ANK-repeat domain differs considerably from those of the intermolecular complexes described above. In the cupped-hand analogy, the transcriptional activator interacts with

Summary

Protein evolution demands conservation of key residues to maintain structural integrity, but allows for sequence variations that, in turn, provide functional specificity. In fact, the complex biochemical requirements of a living cell appear to be largely fulfilled by a relatively small number of protein architectures. In some cases, versatility has been achieved through the assembly of multiple copies of amino acid sequences to form families of structurally related but functionally diverse

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