ArticleStructure (London, England : 1993)2013
Complex energy landscape of a giant repeat protein.
Article in Structure (London, England : 1993), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Small Molecule Activators of Protein Phosphatase 2A Exert Global Stabilizing Effects on the Scaffold PR65.JACS Au · 2026Article
- Small Molecule Activator of Phosphatase PP2A Remodels Scaffold PR65 Structural Dynamics To Promote Holoenzyme Assembly.JACS Au · 2026Article
- Small molecule activator of phosphatase PP2A remodels scaffold PR65 structural dynamics to promote holoenzyme assembly.bioRxiv : the preprint server for biology · 2025Article
- Sphingosine simultaneously inhibits nuclear import and activates PP2A by binding importins and PPP2R1A.The EMBO journal · 2025Article
- Influence of point mutations on PR65 conformational adaptability: Insights from molecular simulations and nanoaperture optical tweezers.Science advances · 2024Article
- Comparative analysis of the LARP1 C-terminal DM15 region through Coelomate evolution.PloS one · 2024Article
- Interaction between huntingtin exon 1 and HEAT repeat structure probed by chimeric model proteins.Protein science : a publication of the Protein Society · 2023Article
- Cooperative mechanics of PR65 scaffold underlies the allosteric regulation of the phosphatase PP2A.Structure (London, England : 1993) · 2023Article
- Nonspecific Amyloid Aggregation of Chicken Smooth-Muscle Titin: In Vitro Investigations.International journal of molecular sciences · 2023Article
- The metaphorical swiss army knife: The multitude and diverse roles of HEAT domains in eukaryotic translation initiation.Nucleic acids research · 2022Review
- Unraveling the Mechanics of a Repeat-Protein Nanospring: From Folding of Individual Repeats to Fluctuations of the Superhelix.ACS nano · 2022Article
- Ycs4 Subunit ofBiochemistry · 2021Article
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- Bioorthogonal protein-DNA conjugation methods for force spectroscopy.Scientific reports · 2019Article
- Folding cooperativity and allosteric function in the tandem-repeat protein class.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2018Review
- Therapeutic targeting of PP2A.The international journal of biochemistry & cell biology · 2018Review
- PyFolding: Open-Source Graphing, Simulation, and Analysis of the Biophysical Properties of Proteins.Biophysical journal · 2018Article
- Establishment of the early cilia preassembly protein complex during motile ciliogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Structural Determinants of Misfolding in Multidomain Proteins.PLoS computational biology · 2016Article
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8 authors.
Funding
Abstract
Here, we reveal a remarkable complexity in the unfolding of giant HEAT-repeat protein PR65/A, a molecular adaptor for the heterotrimeric PP2A phosphatases. The repeat array ruptures at multiple sites, leading to intermediate states with noncontiguous folded subdomains. There is a dominant sequence of unfolding, which reflects a nonuniform stability distribution across the repeat array and can be rationalized by theoretical models accounting for heterogeneous contact density in the folded structure. Unfolding of certain intermediates is, however, competitive, leading to parallel unfolding pathways. The low-stability, central repeats sample unfolded conformations under physiological conditions, suggesting how folding directs function: certain regions present rigid motifs for molecular recognition, whereas others have the flexibility with which to broaden the search area, as in the fly-casting mechanism. Partial unfolding of PR65/A also impacts catalysis by altering the proximity of bound catalytic subunit and substrate. Thus, the repeat array orchestrates the assembly and activity of PP2A.
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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.