ArticleeLife2017
Symmetry broken and rebroken during the ATP hydrolysis cycle of the mitochondrial Hsp90 TRAP1.
Article in eLife, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 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.
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Who cites it
45 citing papers in PubMed, 81 citations in OpenAlex.
- Coordinated regulation of the metaboproteome by Hsp90 chaperones controls metabolic plasticity.iScience · 2026Article
- Nature Counts to Three: Universal Mg-Pinch Motif Polarizes the Cleaved Bond in NTP-Processing Enzymes.Journal of the American Chemical Society · 2026Article
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- New allosteric modulators of molecular chaperone TRAP1 from the integration of computational biology, medicinal chemistry, and biophysics.Cell stress & chaperones · 2026Review
- Supercoiled DNA recognition and cleavage control in topoisomerase VI.Nature communications · 2026Article
- Molecular mechanism of PINK1 regulation by the Hsp90 machinery.Nature communications · 2025Article
- Point mutations of the mitochondrial chaperone TRAP1 affect its functions and pro-neoplastic activity.Cell death & disease · 2025Article
- The known unknowns of the Hsp90 chaperone.eLife · 2024Review
- N-Glycosylation-Induced Pathologic Protein Conformations as a Tool to Guide the Selection of Biologically Active Small Molecules.Chemistry (Weinheim an der Bergstrasse, Germany) · 2024Article
- Antiproliferative Impact of Linagliptin on the Cervical Cancer Cell Line.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Hsp90, a team player in protein quality control and the stress response in bacteria.Microbiology and molecular biology reviews : MMBR · 2024Review
- Heat Shock Proteins and Breast Cancer.International journal of molecular sciences · 2024Review
- How aberrant N-glycosylation can alter protein functionality and ligand binding: An atomistic view.Structure (London, England : 1993) · 2023Article
- Insight into the Nucleotide Based Modulation of the Grp94 Molecular Chaperone Using Multiscale Dynamics.The journal of physical chemistry. B · 2023Article
- Pan-HSP90 ligand binding reveals isoform-specific differences in plasticity and water networks.Protein science : a publication of the Protein Society · 2023Article
- The development of cancers research based on mitochondrial heat shock protein 90.Frontiers in oncology · 2023Review
- The mitochondrial chaperone TRAP1 regulates F-ATP synthase channel formation.Cell death and differentiation · 2022Article
- O-GlcNAcylation suppresses TRAP1 activity and promotes mitochondrial respiration.Cell stress & chaperones · 2022Article
- The Mitochondrial HSP90 Paralog TRAP1: Structural Dynamics, Interactome, Role in Metabolic Regulation, and Inhibitors.Biomolecules · 2022Review
- Non-Equilibrium Protein Folding and Activation by ATP-Driven Chaperones.Biomolecules · 2022Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Hsp90 is a homodimeric ATP-dependent molecular chaperone that remodels its substrate 'client' proteins, facilitating their folding and activating them for biological function. Despite decades of research, the mechanism connecting ATP hydrolysis and chaperone function remains elusive. Particularly puzzling has been the apparent lack of cooperativity in hydrolysis of the ATP in each protomer. A crystal structure of the mitochondrial Hsp90, TRAP1, revealed that the catalytically active state is closed in a highly strained asymmetric conformation. This asymmetry, unobserved in other Hsp90 homologs, is due to buckling of one of the protomers and is most pronounced at the broadly conserved client-binding region. Here, we show that rather than being cooperative or independent, ATP hydrolysis on the two protomers is sequential and deterministic. Moreover, dimer asymmetry sets up differential hydrolysis rates for each protomer, such that the buckled conformation favors ATP hydrolysis. Remarkably, after the first hydrolysis, the dimer undergoes a flip in the asymmetry while remaining in a closed state for the second hydrolysis. From these results, we propose a model where direct coupling of ATP hydrolysis and conformational flipping rearranges client-binding sites, providing a paradigm of how energy from ATP hydrolysis can be used for client remodeling.
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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.