Author response: Hsf1 and Hsp70 constitute a two-component feedback loop that regulates the yeast heat shock response

Krakowiak, Joanna; Xu, Zheng; Patel, Nikit; Feder, Zoë A.; Anandhakumar, Jayamani; Valerius, Kendra; Gross, David S.; Khalil, Ahmad S.; Pincus, David

doi:10.7554/elife.31668.024

Cited by 3 publications

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“…)(Krakowiak et al, 2018;Masser et al, 2019;Peffer et al, 2019;Zheng et al, 2016), so we wondered if Hsp70 binding would also repress HSR condensate formation. To test this, we disrupted the Hsp70 binding site located in the C-terminal segment of Hsf1, known as "conserved element 2" (CE2), by introducing alanine substitutions at residues known to be required for Hsp70 association(Krakowiak et al., 2018; Peffer et al, 2019) (Figure3A, B).…”

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Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response

Chowdhary

Kainth

Paracha

et al. 2021

Preprint

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SUMMARYMammalian developmental and disease-associated genes concentrate large quantities of the transcriptional machinery by forming membrane-less compartments known as transcriptional condensates. However, it is unknown whether these structures are evolutionarily conserved, capable of stress-inducible gene activation or involved in 3D genome reorganization. Here, we identify inducible transcriptional condensates in the yeast heat shock response (HSR). HSR condensates are biophysically dynamic spatiotemporal clusters of the sequence-specific transcription factor Heat shock factor 1 (Hsf1) with Mediator and RNA Pol II. Uniquely, HSR condensates drive the coalescence of multiple Hsf1 target genes, even those located on different chromosomes. Binding of the chaperone Hsp70 to a site on Hsf1 represses clustering, while an intrinsically disordered region on Hsf1 promotes condensate formation and intergenic interactions. Mutation of both Hsf1 determinants reprograms HSR condensates to become mammalian-like: constitutively active without intergenic coalescence. These results suggest that transcriptional condensates are ancient and flexible compartments of eukaryotic gene control.

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Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response

Chowdhary

Kainth

Paracha

et al. 2021

Preprint

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Protein Misfolding Releases Human HSF1 from HSP70 Latency Control

Ciccarelli,

Andréasson

2024

Journal of Molecular Biology

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Comparative modeling and mutual docking of structurally uncharacterized heat shock protein 70 and heat shock factor-1 proteins in water buffalo

et al. 2019

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Aim: In this study, a wide range of in silico investigation of Bubalus bubalis (BB) heat shock protein 70 (HSP70) and heat shock factor-1 (HSF1) has been performed, ranging from sequence evaluation among species to homology modeling along with their docking studies to decipher the interacting residues of both molecules. Materials and Methods: Protein sequences of BB HSP70 and HSF1 were retrieved from NCBI database in FASTA format. Primary and secondary structure prediction were computed using Expasy ProtParam server and Phyre2 server, respectively. TMHMM server was used to identify the transmembrane regions in HSP70. Multiple sequence alignment and comparative analysis of the protein was carried out using MAFFT and visualization was created using ESPript 3.0. Phylogenetic analysis was accomplished by COBALT. Interactions of HSP70 with other proteins were studied using STRING database. Modeller 9.18, RaptorX, Swiss-Modeller, Phyre2, and I-TASSER were utilized to design the three-dimensional structure of these proteins followed by refinement; energy minimization was accomplished using ModRefiner and SPDBV program. Stereochemical quality along with the accuracy of the predicted models and their visualization was observed by PROCHECK program of PDBsum and UCSF Chimera, respectively. ClusPro 2.0 server was accessed for the docking of the receptor protein with the ligand. Results: The lower value of Grand Average of Hydropathy indicates the more hydrophilic nature of HSP70 protein. Value of the instability index (II) classified the protein as stable. No transmembrane region was reported for HSP70 by TMHMM server. Phylogenetic analysis based on multiple sequence alignments (MSAs) by COBALT indicated more evolutionarily closeness of Bos indicus (BI) with Bos taurus as compared to BI and BB. STRING database clearly indicates the HSF1 as one of the interacting molecules among 10 interacting partners with HSP 70. The best hit of 3D model of HSP70 protein and HSF1 was retrieved from I-TASSER and Phyre2, respectively. Interacting residues and type of bonding between both the molecules which were docked by ClusPro 2.0 were decoded by PIC server. Hydrophobic interactions, protein-protein main-chain-side-chain hydrogen bonds, and protein-protein side-chain-side-chain hydrogen bonds were delineated in this study. Conclusion: This is the first-ever study on in silico interaction of HSP70 and HSF1 proteins in BB. Several bioinformatics web tools were utilized to study secondary structure along with comparative modeling, physicochemical properties, and protein-protein interaction. The various interacting amino acid residues of both proteins have been indicated in this study.

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Author response: Hsf1 and Hsp70 constitute a two-component feedback loop that regulates the yeast heat shock response

Cited by 3 publications

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Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response

Inducible transcriptional condensates drive 3D genome reorganization in the heat shock response

Protein Misfolding Releases Human HSF1 from HSP70 Latency Control

Comparative modeling and mutual docking of structurally uncharacterized heat shock protein 70 and heat shock factor-1 proteins in water buffalo

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