InterPro: IPR011990 Tetratricopeptide-like helical

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 [4]. 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.

This domain consists of a multi-helical fold comprised of two curved layers of alpha helices arranged in a regular right-handed superhelix, where the repeats that make up this structure are arranged about a common axis [5]. These superhelical structures present an extensive solvent-accessible surface that is well suited to binding large substrates such as proteins and nucleic acids. This topology has been found with a number of repeats and domains, including the tetratricopeptide repeat (TPR) (found in kinesin light chains, SNAP regulatory proteins, clathrin heavy chains and bacterial aspartyl-phosphate phosphatases), and the pentatricopeptide repeat (PPR) (RNA-processing proteins). The TPR is likely to be an ancient repeat, since it is found in eukaryotes, bacteria and archaea, whereas the PPR repeat is found predominantly in higher plants. The superhelix formed from these repeats can bind ligands at a number of different regions, and has the ability to acquire multiple functional roles [6].