The β6/β7 region of the Hsp70 substrate-binding domain mediates heat-shock response and prion propagation

摘要: Hsp70 is a highly conserved chaperone that in addition to providing essential cellular functions and aiding cell survival following exposure variety of stresses also key modulator prion propagation. composed nucleotide-binding domain (NBD) substrate-binding (SBD). The are tightly regulated through an allosteric communication network coordinates ATPase activity with activity. How conformational changes relate functional change results heat shock prion-related phenotypes poorly understood. Here, we utilised the yeast [PSI +] system, coupled SBD-targeted mutagenesis, investigate how within structural regions SBD result protein translate phenotypic defects propagation ability grow at elevated temperatures. We find variants mutated β6 β7 region defective heat-shock phenotypes, due SBD. Structural analysis mutants identifies potential NBD:SBD interface residues may play important roles signal transduction between domains. As consequence disrupting β6/β7 overall, exhibits including dysregulation activity, reduction refold proteins interaction affinity specific co-chaperones substrates. Our findings properties underpin vivo. A thorough understanding molecular mechanisms regulation modifications for development new drugs targeting therapeutic purposes.