Fig. 3.

Certain clients engage Hsp70 both canonically and non-canonically. A The domain architecture of three client proteins is shown, with known Hsp70-binding sequences displayed. A subset of these sequences is experimentally shown to bind in a nucleotide-independent, non-canonical manner and they are not competitive with canonical, model substrates for binding SBDβ. B Schematic to illustrate that some clients, including α-syn and tau, have both canonical and non-canonical binding motifs, and are able to interact with both the SBDβ and SBDα domains of Hsp70s. Still, the exact binding site of non-canonical peptides is unknown. See text for citations and details