Role of DnaJ G/F-rich Domain in Conformational Recognition and Binding of Protein Substrates*

Myopathy-causing Mutations in an HSP40 Chaperone Disrupt Processing of Specific Client Conformers

“…In the context of a human protein aggregate disorder, our data now emphasize the expanded and crucial role that the G/F domain plays in protein aggregation by acting as the major regulator of substrate and conformer selectivity. This agrees with previous data with the bacterial DnaJ protein (6). Two possibilities might explain the selectivity: either the G/F domain directly binds substrates or it modulates the neighboring J domain and the interaction of this domain with Hsp70.…”

“…All known LGMD1D-associated mutations localize to an eightamino acid stretch within the G/F domain. Disruption of the conserved G/F domain of DNAJB6 and similar DNAJ proteins can alter interactions with substrates, thereby highlighting the importance of the G/F domain (2,6,7). However, it is unclear how this domain modulates HSP40 function and how mutation of this region can cause disease.…”

The C-terminal Helices of Heat Shock Protein 70 Are Essential for J-domain Binding and ATPase Activation

“…Our and previous studies have shown that the G/Frich region is disordered in solution (9). The G/F-rich region of DnaJ is important for stabilizing substrate complex formation (28,33). Our data suggest that the G/F-rich region of HSJ1a does not affect the interaction between HSJ1a and HSP70 and the ATPase activation (supplemental Figs.…”

Chaperone-assisted Excisive Recombination, a Solitary Role for DnaJ (Hsp40) Chaperone in Lysogeny Escape

“…However, DnaJ can bind substrates in vitro and protect them from aggregation independently of DnaK. Such chaperone function of DnaJ is carried out by its central zinc-binding domain, its C-terminal domains, and most likely its glycine-phenylalanine-rich region (46) and is thus unrelated to a functional J-domain (47-49). Although we cannot firmly exclude an involvement of DnaK, our results strongly suggest that stimulation of TorI-mediated excision by DnaJ solely relies on such chaperone functions.…”