ArticleMolecular cell2014
Structural asymmetry in the closed state of mitochondrial Hsp90 (TRAP1) supports a two-step ATP hydrolysis mechanism.
Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 92 papers.
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Who cites it
92 citing papers in PubMed.
- Putrescine-bound structure and multi-temperature crystallography provide new insights into ligand binding and conformational heterogeneity in spermidine synthase.Structural dynamics (Melville, N.Y.) · 2026Article
- Direct single-molecule visualization of Hsp90-mediated relief of an Hsp70-folding block.Science advances · 2026Article
- Evolution of Hsp90 targeting: From stress biology to clinical translation.Cell stress & chaperones · 2026Review
- Structural analysis ofbioRxiv : the preprint server for biology · 2026Article
- HSP90B1 facilitates glioma radiotherapy resistance by regulating RhoC ubiquitin‒proteasome degradation.Genes & diseases · 2026Article
- Ligand-driven modulation of chaperone-cochaperone networks shapes proteostasis outcomes.Protein science : a publication of the Protein Society · 2026Article
- New allosteric modulators of molecular chaperone TRAP1 from the integration of computational biology, medicinal chemistry, and biophysics.Cell stress & chaperones · 2026Review
- Biotinylated Hsp90β-selective inhibitors.Bioorganic & medicinal chemistry letters · 2025Article
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- Point mutations of the mitochondrial chaperone TRAP1 affect its functions and pro-neoplastic activity.Cell death & disease · 2025Article
- Article
- Insects in agricultural greenhouses: a metagenomic analysis of microbes inFrontiers in plant science · 2025Article
- Ordered ATP hydrolysis in the Hsp90 chaperone is regulated by Aha1 and a conserved post-translational modification.Protein science : a publication of the Protein Society · 2025Article
- The dynamic triage interplay of Hsp90 with its chaperone cycle and client binding.Nature communications · 2024Article
- Hsp90, a team player in protein quality control and the stress response in bacteria.Microbiology and molecular biology reviews : MMBR · 2024Review
- Hsp90α and cell death in cancers: a review.Discover oncology · 2024Review
- Structural transitions modulate the chaperone activities of Grp94.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural dynamics of RAF1-HSP90-CDC37 and HSP90 complexes reveal asymmetric client interactions and key structural elements.Communications biology · 2024Article
- Unexpected Single-Ligand Occupancy and Negative Cooperativity in the SARS-CoV-2 Main Protease.Journal of chemical information and modeling · 2024Article
- Domain Architecture Based Methods for Comparative Functional Genomics Toward Therapeutic Drug Target Discovery.Journal of molecular evolution · 2023Review
32 more citing papers are in PubMed but not listed here.
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6 authors.
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Abstract
While structural symmetry is a prevailing feature of homo-oligomeric proteins, asymmetry provides unique mechanistic opportunities. We present the crystal structure of full-length TRAP1, the mitochondrial Hsp90 molecular chaperone, in a catalytically active closed state. The TRAP1 homodimer adopts a distinct, asymmetric conformation, where one protomer is reconfigured via a helix swap at the middle:C-terminal domain (MD:CTD) interface. This interface plays a critical role in client binding. Solution methods validate the asymmetry and show extension to Hsp90 homologs. Point mutations that disrupt unique contacts at each MD:CTD interface reduce catalytic activity and substrate binding and demonstrate that each protomer needs access to both conformations. Crystallographic data on a dimeric NTD:MD fragment suggests that asymmetry arises from strain induced by simultaneous NTD and CTD dimerization. The observed asymmetry provides the potential for an additional step in the ATPase cycle, allowing sequential ATP hydrolysis steps to drive both client remodeling and client release.
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