ArticleProceedings of the National Academy of Sciences of the United States of America2019
Hydrogen exchange reveals Hsp104 architecture, structural dynamics, and energetics in physiological solution.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 35 citations in OpenAlex.
- HDX-MS reveals pH and temperature-responsive regions on AAV capsids and the structural basis for DNA release.Gene therapy · 2025Article
- Design principles to tailor Hsp104 therapeutics.Cell reports · 2024Article
- Probe capsid structure stability and dynamics of adeno-associated virus as an important viral vector for gene therapy by hydrogen-deuterium exchange-mass spectrometry.Protein science : a publication of the Protein Society · 2024Article
- Unveiling the domain-specific and RAS isoform-specific details of BRAF kinase regulation.eLife · 2023Article
- Tuning Hsp104 specificity to selectively detoxify α-synuclein.Molecular cell · 2023Article
- Molecular basis of RanGTP-activated release of Histones H2A-H2B from Importin-9.Structure (London, England : 1993) · 2023Article
- Molecular basis of RanGTP-activated nucleosome assembly with Histones H2A-H2B bound to Importin-9.bioRxiv : the preprint server for biology · 2023Article
- AAA+ proteins: one motor, multiple ways to work.Biochemical Society transactions · 2022Review
- Article
- Complementarity of Hydrogen/Deuterium Exchange Mass Spectrometry and Cryo-Electron Microscopy.Trends in biochemical sciences · 2020Review
- Structural and kinetic basis for the regulation and potentiation of Hsp104 function.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Structural and mechanistic insights into Hsp104 function revealed by synchrotron X-ray footprinting.The Journal of biological chemistry · 2020Article
- Structural Energy Landscapes and Plasticity of the Microstates of ApoBiochemistry · 2020Article
- Interpretation of medium resolution cryoEM maps of multi-protein complexes.Current opinion in structural biology · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Hsp104 is a large AAA+ molecular machine that can rescue proteins trapped in amorphous aggregates and stable amyloids by drawing substrate protein into its central pore. Recent cryo-EM studies image Hsp104 at high resolution. We used hydrogen exchange mass spectrometry analysis (HX MS) to resolve and characterize all of the functionally active and inactive elements of Hsp104, many not accessible to cryo-EM. At a global level, HX MS confirms the one noncanonical interprotomer interface in the Hsp104 hexamer as a marker for the spiraled conformation revealed by cryo-EM and measures its fast conformational cycling under ATP hydrolysis. Other findings enable reinterpretation of the apparent variability of the regulatory middle domain. With respect to detailed mechanism, HX MS determines the response of each Hsp104 structural element to the different bound adenosine nucleotides (ADP, ATP, AMPPNP, and ATPγS). They are distinguished most sensitively by the two Walker A nucleotide-binding segments. Binding of the ATP analog, ATPγS, tightly restructures the Walker A segments and drives the global open-to-closed/extended transition. The global transition carries part of the ATP/ATPγS-binding energy to the somewhat distant central pore. The pore constricts and the tyrosine and other pore-related loops become more tightly structured, which seems to reflect the energy-requiring directional pull that translocates the substrate protein. ATP hydrolysis to ADP allows Hsp104 to relax back to its lowest energy open state ready to restart the cycle.
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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.