Updated project metadata.
J-domain proteins tune the specificity of Hsp70s, engaging them in precise functions. Despite their essential role, the structure and function of many J-domain proteins remain largely unknown. We explore human DNAJA2, a class A J-domain protein, finding that it reversibly oligomerises into highly-ordered, tubular structures that can be dissociated by Hsc70, the constitutively expressed Hsp70 isoform. Cryoelectron microscopy and mutational studies reveal that multivalent interactions between different domains are involved in self-association. Oligomer dissociation into dimers potentiates its interaction with unfolded client proteins. Closely spaced J domains in the tubular structure could allow transfer of several Hsc70 molecules to cooperatively remodel the unfolded substrate, explaining the efficient recovery of DNAJA2-bound clients. The disordered C-terminal domain, comprising the last 52 residues, regulates its holding activity and productive interaction with Hsc70. These in vitro findings suggest that the association equilibrium of DNAJA2 could regulate its interaction with client proteins and Hsc70.