25-30 August 2019
Henry Ford Building
Europe/Berlin timezone

The True Tales of the Flexible Tails – Interaction of J-domain Protein with Hsp70 chaperones

28 Aug 2019, 10:30
Lecture Hall C (Henry Ford Building)

Lecture Hall C

Henry Ford Building

Invited talk Biological applications Biomolecules


Dr Rina Rosenzweig (Weizmann Institute of Science)


Hsp70s are ubiquitous chaperones tasked with safeguarding proteins throughout their entire lifecycle, from synthesis to degradation, and are thus critical for maintaining protein-homeostasis. The ATPase cycle of Hsp70s, which is allosterically coupled to the binding and release of their substrates, is, in turn, regulated by a large set of dedicated co-chaperones consisting of nucleotide-exchange-factors and of J-domain proteins. Humans contain multiple such J-domain-proteins(JDPs), all of which interact through their conserved J-domain with Hsp70s in an ATP dependent manner. The most abundant JDPs in the cell belong to very structurally-similar Class-A and Class-B families and contain, in addition to the J‐domain, an adjacent glycine‐rich-region, two client binding domains (CTDI and CTDII), and a dimerization domain.
Despite the many similarities, however, Class-A and Class-B J‐proteins still exhibit significant differences in both structure and function. We were, therefore interested to see whether the two classes of JDPs also display differences in their interactions with Hsp70 chaperones.
To this end, we used solution NMR spectroscopy to test the interaction of Hsc70 with the two classes of DnaJ chaperones, and monitored DnaJ-dependent Hsc70 activation via functional assays.

Our results uncover that Class-A and Class-B DnaJs, in fact, interact with Hsc70 in a different manner. While both classes of DnaJs bind Hsc70 through their J-domain, with this weak interaction activating Hsc70 catalytic activity, Class-B DnaJs also contain an additional Hsc70 binding site. When in complex with Hsc70, we have identified that DnaJB1 interacts both via its N-terminal J-domain and its CTDI substrate-binding-domain. The binding of the Hsc70 C-terminal region to DnaJB1 CTDI causes a conformational change that exposes the DnaJB1 J-domain for Hsc70 binding, with only this second interaction leading to activation of Hsc70 catalytic activity. This, then points to a new regulatory interaction between class-B DnaJ chaperones and Hsc70, that is absent in class-A DnaJs.

Primary author

Dr Rina Rosenzweig (Weizmann Institute of Science)

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