Abstract
The molecular chaperones HSP70 and HSP90 play key roles in proteostasis by acting as adapters; they bind to a 'client' protein, often with the assistance of cochaperones, and then recruit additional cochaperones that promote specific fates (e.g., folding or degradation). One family of cochaperones contains a region termed the tetratricopeptide repeat with carboxylate clamps (CC-TPRs) domain. These domains bind to an EEVD motif at the C-termini of cytoplasmic HSP70 and HSP90 proteins, bringing them into proximity to chaperone-bound clients. It has recently become clear that CC-TPR proteins also bind to 'EEVD-like' motifs in non-chaperone proteins, circumventing the need for HSP70s or HSP90s. We provide an overview of the chaperone-dependent and -independent roles of CC-TPR proteins and discuss how, together, they shape proteostasis.