Tetratricopeptide repeats TPRs

Das, a. K., P. W. Cohen, and D. Bareord, The structure of the tetratricopeptide repeats of protein phosphatase 5 implications for TPR-mediated protein-protein interactions. EmboJ, 1998, 17(5), 1192-9. 

Fig. 5. Domain structure of Hsp70 co-chaperones. Individual domains/modules are represented by differendy shaded boxes. The known structural features and functions of domains are indicated. The following abbreviations for the different domains were used NLS, nuclear localization sequence TRSEEX, Thr-Arg-Ser-Glu-Glu-Xaa repeat motif Ub, ubiquitin-like domain Bag, Bag homology region WW, Trp-Trp domain TPR, tetratricopeptide repeat GGMP, Gly-Gly-Met-Pro repeat motif +/—, charged region U box, U box motif of E4 ubiquitin ligases DnaK, interaction site for DnaK 70, interaction site for Hsp70 90, interaction site for Hsp90.

The most prominent structural feature of Tfc4 is its 11 tetratricopeptide repeats (Marek et al., 1993 Rameau et al., 1994). TPRs are ubiquitous elements of protein structure that function as sites of protein-protein interaction (Lamb et al., 1995). The motif is defined by a degenerate sequence, usually 34 amino acids in length, that is most often found in tandem arrays (Lamb et al., 1995). Individual TPRs fold into two antiparallel a-helices, designated A and B, which are separated by a short turn. The helices within each repeat stack together with helices in adjacent... 

We have previously shown that a 209 amino acid region (aa288-497, asymmetric localization domain) of Insc is necessary and sufficient for apical cortical localization and for mitotic spindle orientation along the apical-basal axis (Tio et al 1999). In a yeast two-hybrid screen we identified Partner of Inscuteable (Pins), a novel 658aa protein with multiple repeats of the Tetratricopeptide (TPR) motif. Affinity purification experiments using embryonic extracts demonstrate that Pins complexes with Insc in vivo. In vitro protein interaction assays demonstrates that Pins interacts with the Insc asymmetric localization domain (see Yu et al 2000). 

The crystal structure of the peptide substrate-binding domain (140—245 of 517 residues of human al subunit) of the human type I enzyme forms 2.5 tetratricopeptide (TPR) repeat domains with five a helices (PDB accession number ITJC). The organization of tyrosine residues is suggested to be key to its interaction with the substrate peptide in a polyproline II helix. The TPR motif is composed of a 34 amino acid repeated a helical motif, and is typically involved in protein-protein interactions. The tandem repeats of TPR motifs are found in many proteins related to chaperone, cell cycle, transcription, and protein transport... 

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