Co-chaperones are helper interacting proteins that modulate the chaperone cycle, being involved in substrate specificity and stimulation of chaperone activity of HSP90/70 and include other heat shock proteins, TPR containing proteins, cyclophilins and others. The TPR containing proteins possess an N-terminal TPR domain, which are more closely related to each other than to TPR domains from other proteins with different functionality [, ], which is involved in HSP90/70 direct interaction. The first N-terminal residues prior to the TRP domain and the C-terminal domain are involved and important for domain interplay and stabilisation of its interactions []. The Hsp90 chaperone machinery in eukaryotes comprises a number of distinct accessory factors, among them TTC4 from human and its homologues Cns1 from yeast and Dpit47 from Drosophila, structurally and functionally conserved from yeast to human. Cns1 is one of the few essential co-chaperones in yeast, important for maintaining translation elongation, specifically chaperoning the elongation factor eEF2. Cns1 interacts with Hgh1 and forms a quaternary complex together with eEF2 and Hsp90 mediating the proper folding and solubility of eEF2. Recently, the C-terminal structure has been solved and is called the "wheel"domain according to its 2D projection. It shows an overall fold consisting of a twisted five-stranded beta sheet surrounded by several alpha helices [].This entry represents the wheel domain found at the C terminus of yeast Cns1, human TTC4 and Drosophila Dpit47 proteins.
