Tetratricopeptide repeat (TPR) domains and TPR-like domains are widespread across nature. They are involved in varied cellular processes and have been traditionally associated with binding to short linear peptide motifs. However, examples of a much more diverse range of molecular recognition modes are increasing year by year. The Protein Data Bank has an ever-expanding collection of TPR proteins in complex with a myriad of different partners, ranging from short linear peptide motifs to large globular protein domains. In this review, we explore these varied binding modes. Additionally, we hope to highlight an emerging property of this simple, malleable fold-the potential for programmable complexity that can be achieved by acting as a scaffold for multiple binding partners.
