InterPro domain: IPR019734

The tetratrico peptide repeat region (TPR) is a structural motif present in a wide range of proteins [ 1 , 2 , 3 ]. It mediates protein-protein interactions and the assembly of multiprotein complexes [ 4 ]. The TPR motif consists of 3-16 tandem-repeats of 34 amino acids residues, although individual TPR motifs can be dispersed in the protein sequence. Sequence alignment of the TPR domains reveals a consensus sequence defined by a pattern of small and large amino acids. TPR motifs have been identified in various different organisms, ranging from bacteria to humans. Proteins containing TPRs are involved in a variety of biological processes, such as cell cycle regulation, transcriptional control, mitochondrial and peroxisomal protein transport, neurogenesis and protein folding.

The X-ray structure of a domain containing three TPRs from protein phosphatase 5 revealed that TPR adopts a helix-turn-helix arrangement, with adjacent TPR motifs packing in a parallel fashion, resulting in a spiral of repeating anti-parallel alpha-helices [ 5 ]. The two helices are denoted helix A and helix B. The packing angle between helix A and helix B is ~24 degrees within a single TPR and generates a right-handed superhelical shape. Helix A interacts with helix B and with helix A' of the next TPR. Two protein surfaces are generated: the inner concave surface is contributed to mainly by residue on helices A, and the other surface presents residues from both helices A and B.

1. Tetratrico peptide repeat interactions: to TPR or not to TPR? Trends Biochem. Sci. 20, 257-9
2. The structure of the tetratricopeptide repeats of protein phosphatase 5: implications for TPR-mediated protein-protein interactions. EMBO J. 17, 1192-9
3. The TPR snap helix: a novel protein repeat motif from mitosis to transcription. Trends Biochem. Sci. 16, 173-7
4. TPR proteins: the versatile helix. Trends Biochem. Sci. 28, 655-62