Hassan AQ~Sadlish H, 2015

Pubmed ID 25544045
Title The novolactone natural product disrupts the allosteric regulation of Hsp70.
Authors A Quamrul Hassan, Christina A Kirby, Wenlai Zhou, Tim Schuhmann, Roman Kityk, D Randal Kipp, Jason Baird, Jinyun Chen, Yaoyu Chen, Franklin Chung, Dominic Hoepfner, N Rao Movva, Raymond Pagliarini, Frank Petersen, Christopher Quinn, Douglas Quinn, Ralph Riedl, Esther K Schmitt, Anne Schitter, Travis Stams, Christian Studer, Pascal D Fortin, Matthias P Mayer, Heather Sadlish
Abstract The highly conserved 70 kDa heat shock proteins (Hsp70) play an integral role in proteostasis such that dysregulation has been implicated in numerous diseases. Elucidating the precise role of Hsp70 family members in the cellular context, however, has been hampered by the redundancy and intricate regulation of the chaperone network, and relatively few selective and potent tools. We have characterized a natural product, novolactone, that targets cytosolic and ER-localized isoforms of Hsp70 through a highly conserved covalent interaction at the interface between the substrate-binding and ATPase domains. Biochemical and structural analyses indicate that novolactone disrupts interdomain communication by allosterically inducing a conformational change in the Hsp70 protein to block ATP-induced substrate release and inhibit refolding activities. Thus, novolactone is a valuable tool for exploring the requirements of Hsp70 chaperones in diverse cellular contexts.
Citation Chem. Biol. 2015; 22:87-97

Datasets

Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Hassan AQ~Sadlish H, 2015 novolactone [unknown] het N/A None
Hassan AQ~Sadlish H, 2015 novolactone [unknown] hom N/A None

Curation history

Data

Feb. 20, 2019 To request.
March 27, 2019 Request sent.
March 27, 2019 Not available.

Tested strains

Feb. 20, 2019 To request.
March 27, 2019 Request sent.
March 27, 2019 Not available.