ArticleScience advances2021
Ultrafast pore-loop dynamics in a AAA+ machine point to a Brownian-ratchet mechanism for protein translocation.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Benchmarking dynamic analysis methods in diffusion-based single-molecule FRET.Cell reports methods · 2026Article
- A stochastic mechanism drives fast substrate translocation in the AAA+ machine ClpB.Nature communications · 2026Article
- Structure of the central Staphylococcus aureus AAA+ protease MecA/ClpC/ClpP.Communications biology · 2025Article
- Quantitative analysis methods for free diffusion single-molecule FRET experiments.Current opinion in structural biology · 2025Review
- Mapping Hsp104 interactions using cross-linking mass spectrometry.FEBS open bio · 2025Article
- Quantitative insights into processivity of an Hsp100 protein disaggregase on folded proteins.Biophysical journal · 2025Article
- Unmasking AlphaFold to integrate experiments and predictions in multimeric complexes.Nature communications · 2024Article
- Single turnover transient state kinetics reveals processive protein unfolding catalyzed byeLife · 2024Article
- Motif-VI loop acts as a nucleotide valve in the West Nile Virus NS3 Helicase.Nucleic acids research · 2024Article
- Single-molecule FRET probes allosteric effects on protein-translocating pore loops of a AAA+ machine.Biophysical journal · 2024Article
- From Microstates to Macrostates in the Conformational Dynamics of GroEL: A Single-Molecule Förster Resonance Energy Transfer Study.The journal of physical chemistry letters · 2023Article
- Perspective: How Fast Dynamics Affect Slow Function in Protein Machines.The journal of physical chemistry. B · 2023Review
- Article
- Single-Molecule Optical Tweezers As a Tool for Delineating the Mechanisms of Protein-Processing Mechanoenzymes.ACS omega · 2023Review
- Deciphering the mechanism and function of Hsp100 unfoldases from protein structure.Biochemical Society transactions · 2022Article
- Experimental study of a nanoscale translocation ratchet.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Insights into the Structure and Function of the Pex1/Pex6 AAA-ATPase in Peroxisome Homeostasis.Cells · 2022Review
- Hydrodynamic synchronization and clustering in ratcheting colloidal matter.Science advances · 2022Article
- Exploring the Effect of Mechanical Anisotropy of Protein Structures in the Unfoldase Mechanism of AAA+ Molecular Machines.Nanomaterials (Basel, Switzerland) · 2022Article
- AAA+ proteins: one motor, multiple ways to work.Biochemical Society transactions · 2022Review
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Authors and funding
4 authors.
Funding
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Abstract
AAA+ ring–shaped machines, such as the disaggregation machines ClpB and Hsp104, mediate ATP-driven substrate translocation through their central channel by a set of pore loops. Recent structural studies have suggested a universal hand-over-hand translocation mechanism with slow and rigid subunit motions. However, functional and biophysical studies are in discord with this model. Here, we directly measure the real-time dynamics of the pore loops of ClpB during substrate threading, using single-molecule FRET spectroscopy. All pore loops undergo large-amplitude fluctuations on the microsecond time scale and change their conformation upon interaction with substrate proteins in an ATP-dependent manner. Conformational dynamics of two of the pore loops strongly correlate with disaggregation activity, suggesting that they are the main contributors to substrate pulling. This set of findings is rationalized in terms of an ultrafast Brownian-ratchet translocation mechanism, which likely acts in parallel to the much slower hand-over-hand process in ClpB and other AAA+ machines.
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