ArticleCommunications biology2021
Conformational dynamics of free and membrane-bound human Hsp70 in model cytosolic and endo-lysosomal environments.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Lipid-gated vesicular trafficking directs HSPA1A to the plasma membrane through the endo-lysosomal network.Cell stress & chaperones · 2026Article
- Physical exercise in combination with audiovisual stimulation alleviates cognitive and affective impairments in Alzheimer's disease model mice via restoring lysosomal membrane integrity.Alzheimer's research & therapy · 2026Article
- Structural dynamics and immunogenicity of the recombinant and outer membrane vesicle-embedded Meningococcal antigen NadA.Nature communications · 2026Article
- Assessment of bis(monoacylglycerol)phosphate isomers by thin layer chromatography using a modified solvent system.Biochemistry and biophysics reports · 2025Article
- Lysosomal Repair in Health and Disease.Journal of cellular physiology · 2025Review
- Single-molecule study of the dynamics of the molecular chaperone Hsp70 during the functional cycle.Biochemical Society transactions · 2025Review
- The Confluence of Nanotechnology and Heat Shock Protein 70 in Pioneering Glioblastoma Multiforme Therapy: Forging Pathways Towards Precision Targeting and Transformation.Advances in pharmacological and pharmaceutical sciences · 2025Review
- Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein.Nature communications · 2023Article
- Externally Applied Electromagnetic Fields and Hyperthermia Irreversibly Damage Cancer Cells.Cancers · 2023Article
- Chromatographic Phospholipid Trapping for Automated H/D Exchange Mass Spectrometry of Membrane Protein-Lipid Assemblies.Analytical chemistry · 2023Article
- Probing Antibody Structures by Hydrogen/Deuterium Exchange Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The binding of the major stress-inducible human 70-kDa heat shock protein (Hsp70) to the anionic phospholipid bis-(monoacylglycero)-phosphate (BMP) in the lysosomal membrane is crucial for its impact on cellular pathology in lysosomal storage disorders. However, the conformational features of this protein-lipid complex remain unclear. Here, we apply hydrogen-deuterium exchange mass spectrometry (HDX-MS) to describe the dynamics of the full-length Hsp70 in the cytosol and its conformational changes upon translocation into lysosomes. Using wild-type and W90F mutant proteins, we also map and discriminate the interaction of Hsp70 with BMP and other lipid components of the lysosomal membrane. We identify the N-terminal of the nucleotide binding domain (residues 87-118) as the primary orchestrator of BMP interaction. We show that the conformation of this domain is significantly reorganized in the W90F mutant, explaining its inability to stabilize lysosomal membranes. Overall, our results reveal important new molecular details of the protective effect of Hsp70 in lysosomal storage diseases, which, in turn, could guide future drug development.
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