ArticleThe Journal of biological chemistry2016
Crowding Activates Heat Shock Protein 90.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- Macromolecular Crowding in Cell Stress and Death.Sub-cellular biochemistry · 2025Review
- Recent Advances in DNA Origami-Enabled Optical Biosensors for Multi-Scenario Application.Nanomaterials (Basel, Switzerland) · 2024Review
- Cell stress and phase separation stabilize the monomeric state of pseudoisocyanine chloride employed as a self-assembly crowding sensor.Communications chemistry · 2024Article
- Structural transitions modulate the chaperone activities of Grp94.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural and functional complexity of HSP90 in cellular homeostasis and disease.Nature reviews. Molecular cell biology · 2023Review
- The endoplasmic reticulum chaperone BiP is a closure-accelerating cochaperone of Grp94.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Article
- Plasmodium falciparum R2TP complex: driver of parasite Hsp90 function.Biophysical reviews · 2019Review
- Conformational Cycling within the Closed State of Grp94, an Hsp90-Family Chaperone.Journal of molecular biology · 2019Article
- Effect of Macromolecular Crowding on the FMN-Heme Intraprotein Electron Transfer in Inducible NO Synthase.Biochemistry · 2019Article
- The endoplasmic reticulum (ER) chaperones BiP and Grp94 selectively associate when BiP is in the ADP conformation.The Journal of biological chemistry · 2019Article
- Large cosolutes, small cosolutes, and dihydrofolate reductase activity.Protein science : a publication of the Protein Society · 2017Article
- Hsp90 Sensitivity to ADP Reveals Hidden Regulation Mechanisms.Journal of molecular biology · 2017Article
- 5'-N-ethylcarboxamidoadenosine is not a paralog-specific Hsp90 inhibitor.Protein science : a publication of the Protein Society · 2016Article
- In Vivo Conformational Dynamics of Hsp90 and Its Interactors.Cell chemical biology · 2016Article
- Making microenvironments: A look into incorporating macromolecular crowding into in vitro experiments, to generate biomimetic microenvironments which are capable of directing cell function for tissue engineering applications.Journal of tissue engineeringArticle
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Hsp90 is a dimeric ATP-dependent chaperone involved in the folding, maturation, and activation of diverse target proteins. Extensive in vitro structural analysis has led to a working model of Hsp90's ATP-driven conformational cycle. An implicit assumption is that dilute experimental conditions do not significantly perturb Hsp90 structure and function. However, Hsp90 undergoes a dramatic open/closed conformational change, which raises the possibility that this assumption may not be valid for this chaperone. Indeed, here we show that the ATPase activity of Hsp90 is highly sensitive to molecular crowding, whereas the ATPase activities of Hsp60 and Hsp70 chaperones are insensitive to crowding conditions. Polymer crowders activate Hsp90 in a non-saturable manner, with increasing efficacy at increasing concentration. Crowders exhibit a non-linear relationship between their radius of gyration and the extent to which they activate Hsp90. This experimental relationship can be qualitatively recapitulated with simple structure-based volume calculations comparing open/closed configurations of Hsp90. Thermodynamic analysis indicates that crowding activation of Hsp90 is entropically driven, which is consistent with a model in which excluded volume provides a driving force that favors the closed active state of Hsp90. Multiple Hsp90 homologs are activated by crowders, with the endoplasmic reticulum-specific Hsp90, Grp94, exhibiting the highest sensitivity. Finally, we find that crowding activation works by a different mechanism than co-chaperone activation and that these mechanisms are independent. We hypothesize that Hsp90 has a higher intrinsic activity in the cell than in vitro.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.