ArticleScientific reports2017
Hsp90 dependence of a kinase is determined by its conformational landscape.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 26 citations in OpenAlex.
- Hsp90 inhibition leads to an increase in surface expression of multiple immunological receptors in cancer cells.Frontiers in molecular biosciences · 2024Article
- The cardiac glycoside ZINC253504760 induces parthanatos-type cell death and G2/M arrest via downregulation of MEK1/2 phosphorylation in leukemia cells.Cell biology and toxicology · 2023Article
- How aberrant N-glycosylation can alter protein functionality and ligand binding: An atomistic view.Structure (London, England : 1993) · 2023Article
- Molecular determinants of Hsp90 dependence of Src kinase revealed by deep mutational scanning.Protein science : a publication of the Protein Society · 2023Article
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- Disrupting progression of the yeast Hsp90 folding pathway at different transition points results in client-specific maturation defects.Genetics · 2021Article
- Aspergillus fumigatus Hsp90 interacts with the main components of the cell wall integrity pathway and cooperates in heat shock and cell wall stress adaptation.Cellular microbiology · 2021Article
- Article
- Chaperoning STAT3/5 by Heat Shock Proteins: Interest of Their Targeting in Cancer Therapy.Cancers · 2019Review
- Autophosphorylation activates c-Src kinase through global structural rearrangements.The Journal of biological chemistry · 2019Article
- Selective Proteolysis to Study the Global Conformation and Regulatory Mechanisms of c-Src Kinase.ACS chemical biology · 2019Article
- Therapeutic Potential of the Hsp90/Cdc37 Interaction in Neurodegenerative Diseases.Frontiers in neuroscience · 2019Review
- Dissecting Structure-Encoded Determinants of Allosteric Cross-Talk between Post-Translational Modification Sites in the Hsp90 Chaperones.Scientific reports · 2018Article
- Catalytic mechanism and molecular engineering of quinolone biosynthesis in dioxygenase AsqJ.Nature communications · 2018Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heat shock protein 90 (Hsp90) is an abundant molecular chaperone, involved in the folding and activation of 60% of the human kinome. The oncogenic tyrosine kinase v-Src is one of the most stringent client proteins of Hsp90, whereas its almost identical homolog c-Src is only weakly affected by the chaperone. Here, we perform atomistic molecular simulations and in vitro kinase assays to explore the mechanistic differences in the activation of v-Src and c-Src. While activation in c-Src is strictly controlled by ATP-binding and phosphorylation, we find that activating conformational transitions are spontaneously sampled in Hsp90-dependent Src mutants. Phosphorylation results in an enrichment of the active conformation and in an increased affinity for Hsp90. Thus, the conformational landscape of the mutated kinase is reshaped by a broken "control switch", resulting in perturbations of long-range electrostatics, higher activity and increased Hsp90-dependence.
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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.