The tandem β-zipper: modular binding of tandem domains and linear motifs

Abstract

The tandem β-zipper protein-protein binding interface involves an intrinsically disordered protein (IDP) binding two or more globular domains through β-sheet-augmentation in a modular fashion, and represents a paradigm in IDP-mediated protein-protein interactions. While characterised tandem β-zippers are rare, known examples are associated with diverse biological processes. A combination of their advantages (binding specificity and the ability to generate high affinity binding sites by linking multiple lower affinity motifs) and the prevalence of both tandem domains and IDPs points to the existence of many more β-zippers in nature. The characterisation of these interactions has greatly enhanced the understanding of the biological systems involved but given their apparent tolerance to mutation, detecting other tandem β-zipper interactions using bioinformatics may be challenging.