ArticleJournal of molecular biology2009
pH-dependent conformational changes in bacterial Hsp90 reveal a Grp94-like conformation at pH 6 that is highly active in suppression of citrate synthase aggregation.
Article in Journal of molecular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 60 citations in OpenAlex.
- Nitration-driven structural changes in Hsp90 linked to gain of pathological functions.The Biochemical journal · 2025Article
- Structural transitions modulate the chaperone activities of Grp94.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Insight into the Nucleotide Based Modulation of the Grp94 Molecular Chaperone Using Multiscale Dynamics.The journal of physical chemistry. B · 2023Article
- Structural Communication between theInternational journal of molecular sciences · 2021Article
- Stimulation of heat shock protein 90 chaperone function through binding of a novobiocin analog KU-32.The Journal of biological chemistry · 2019Article
- Hsp90 and Hsp70 chaperones: Collaborators in protein remodeling.The Journal of biological chemistry · 2019Review
- Hsp90 Sensitivity to ADP Reveals Hidden Regulation Mechanisms.Journal of molecular biology · 2017Article
- Symmetry broken and rebroken during the ATP hydrolysis cycle of the mitochondrial Hsp90 TRAP1.eLife · 2017Article
- Molecular mechanism of bacterial Hsp90 pH-dependent ATPase activity.Protein science : a publication of the Protein Society · 2017Article
- Article
- A pH- and ionic strength-dependent conformational change in the neck region regulates DNGR-1 function in dendritic cells.The EMBO journal · 2016Article
- A review of multi-domain and flexible molecular chaperones studies by small-angle X-ray scattering.Biophysical reviews · 2016Review
- Crowding Activates Heat Shock Protein 90.The Journal of biological chemistry · 2016Article
- Article
- Hsp70 and Hsp90 of E. coli Directly Interact for Collaboration in Protein Remodeling.Journal of molecular biology · 2015Article
- Elucidating the mechanism of substrate recognition by the bacterial Hsp90 molecular chaperone.Journal of molecular biology · 2014Article
- Computational modeling of allosteric regulation in the hsp90 chaperones: a statistical ensemble analysis of protein structure networks and allosteric communications.PLoS computational biology · 2014Article
- Structural asymmetry in the closed state of mitochondrial Hsp90 (TRAP1) supports a two-step ATP hydrolysis mechanism.Molecular cell · 2014Article
- Differences in conformational dynamics within the Hsp90 chaperone family reveal mechanistic insights.Frontiers in molecular biosciences · 2014Article
- Uncovering a region of heat shock protein 90 important for client binding in E. coli and chaperone function in yeast.Molecular cell · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The molecular chaperone Hsp90 depends upon large conformational rearrangements for its function. One driving force for these rearrangements is the intrinsic ATPase activity of Hsp90, as seen with other chaperones. However, unlike other chaperones, structural and kinetic studies have shown that the ATPase cycle of Hsp90 is not conformationally deterministic. That is, rather than dictating the conformational state, ATP binding and hydrolysis shift the equilibrium between a preexisting set of conformational states in an organism-dependent manner. While many conformations of Hsp90 have been described, little is known about how they relate to chaperone function. In this study, we show that the conformational equilibrium of the bacterial Hsp90, HtpG, can be shifted with pH. Using small-angle X-ray scattering, we identify a two-state pH-dependent conformational equilibrium for apo HtpG. Our structural modeling reveals that this equilibrium is observed between the previously observed extended state and a second state that is strikingly similar to the recently solved Grp94 crystal structure. In the presence of nonhydrolyzable 5'-adenylyl-beta,gamma-imidodiphosphate, a third state, which is identical with the solved AMPPNP-bound structure from yeast Hsp90, is populated. Electron microscopy confirmed the observed conformational equilibria. We also identify key histidine residues that control this pH-dependent equilibrium; using mutagenesis, we successfully modulate the conformational equilibrium at neutral pH. Using these mutations, we show that the Grp94-like state provides stronger aggregation protection compared to the extended apo conformation in the context of a citrate synthase aggregation assay. These studies provide a more detailed view of HtpG's conformational dynamics and provide the first linkage between a specific conformation and chaperone function.
Indexed as
Identifiers
What OpenQuestion holds
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.