TPR Protein Domain

The amino-terminal TPR domain of human Hop bound to a carboxy-terminal peptide from Hsp70 (red).

Domain Binding and Function

The tetratricopeptide repeat (TPR) motif was originally identified in yeast as a protein-protein interaction module in cell cycle proteins. It has since been found in organisms ranging from bacteria to humans. The TPR motif is a degenerate sequence of ~34 amino acids loosely based around the consensus residues -W-LG-Y-A-F-A-P-. The sequence occurs in tandem arrays and is present in over 800 different proteins. TPR motif-containing proteins act as scaffolds for the assembly of different multiprotein complexes including the anaphase promoting, the peroxisomal import receptor and the NADPH oxidase complexes.

Structure

TPR motifs exhibit a large degree of sequence diversity. However, structural comparison reveals a highly conserved three-dimensional structure. Individual TPR domains are composed of two anti-parallel α helices separated by a turn. Multiple TPR domains arrange at regular angles and form a right-handed super helix. This creates a groove with a large amount of surface area available for ligand binding.

Structure Reference

Scheufler, C. et al. (2000) Cell 101(2), 199–210.

Examples of Domain Proteins

Binding Examples

TPR Domain Proteins	Binding Partners	Peptide Ligands
PEX5	PTS-1 target signal	S-K-L-COOH
Hop	Hsp70 - C-term heptapeptide Hsp90 - C-term pentapeptide	E-E-V-D-COOH E-E-V-D-COOH
p67^phox	GTP-Rac	surface contacts