ArticleScience (New York, N.Y.)2016
Atomic structure of Hsp90-Cdc37-Cdk4 reveals that Hsp90 traps and stabilizes an unfolded kinase.
Article in Science (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 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
237 citing papers in PubMed, 436 citations in OpenAlex.
- Eupalinolide B Ameliorates Diabetic Kidney Disease via Inhibition of Cell Division Cycle 37-Mediated Inflammatory Pathways.Journal of the American Society of Nephrology : JASN · 2026Article
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- Symbiont-Induced HSP83 Establishes Two-Tiered Control of Antifungal Immunity in an Invasive Beetle-Fungus Complex.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Direct single-molecule visualization of Hsp90-mediated relief of an Hsp70-folding block.Science advances · 2026Article
- Post-Translational Modification as an Allosteric Switch in Hsp90: How Dual Phosphorylation Locks Chaperone Complexes into Hyperstabilized States.The journal of physical chemistry letters · 2026Article
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- Hsp90: A means to an end.Cell stress & chaperones · 2026Review
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- Inherent MS-cleavability of diazirine photo-cross-links enables residue-level structural analysis.Nature communications · 2026Article
- Comparative analysis of the impact of Heat shock protein 90 kDa or Cdc37 mutation on the yeast proteome.Cell stress & chaperones · 2026Article
- CDK4/6 Inhibitors for Breast Cancer Therapy-A Review of Clinical Trials, Structural and Computational Approaches.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Article
- Molecular mechanism of PINK1 regulation by the Hsp90 machinery.Nature communications · 2025Article
- Design of multi-target peptide modulators for protein chaperone networks.Structure (London, England : 1993) · 2025Article
- Serine/Threonine Kinase 33 as a Novel Target of Bufalin in Treatment of Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Conformational plasticity of a BiP-GRP94 chaperone complex.Nature structural & molecular biology · 2025Article
- ATP plays a structural role in Hsp90 function.Nature communications · 2025Article
- The Fascinating Intricacy of pSer/Thr-Specific Phosphatases and Their Higher-Order Complexes: Emerging Concepts.Biochemistry · 2025Review
- Purification and characterization of full-length monomeric TEC family kinase, ITK.Protein expression and purification · 2025Article
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
177 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The Hsp90 molecular chaperone and its Cdc37 cochaperone help stabilize and activate more than half of the human kinome. However, both the mechanism by which these chaperones assist their "client" kinases and the reason why some kinases are addicted to Hsp90 while closely related family members are independent are unknown. Our structural understanding of these interactions is lacking, as no full-length structures of human Hsp90, Cdc37, or either of these proteins with a kinase have been elucidated. Here we report a 3.9 angstrom cryo-electron microscopy structure of the Hsp90-Cdc37-Cdk4 kinase complex. Surprisingly, the two lobes of Cdk4 are completely separated with the β4-β5 sheet unfolded. Cdc37 mimics part of the kinase N lobe, stabilizing an open kinase conformation by wedging itself between the two lobes. Finally, Hsp90 clamps around the unfolded kinase β5 strand and interacts with exposed N- and C-lobe interfaces, protecting the kinase in a trapped unfolded state. On the basis of this structure and an extensive amount of previously collected data, we propose unifying conceptual and mechanistic models of chaperone-kinase interactions.
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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.