ArticleThe EMBO journal2020
Autonomous aggregation suppression by acidic residues explains why chaperones favour basic residues.
Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Employing deep mutational scanning in theProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Chemical Synthesis of Medin via a Removable Aggregation-Suppressing Linker.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- GArNet: A Genetic Algorithm-Based Protein Redesign Approach to Optimize Mutation Combinations Informed by Network Theory.Journal of chemical information and modeling · 2025Article
- Co-translational protein aggregation and ribosome stalling as a broad-spectrum antibacterial mechanism.Nature communications · 2025Article
- CsgA gatekeeper residues control nucleation but not stability of functional amyloid.Protein science : a publication of the Protein Society · 2024Article
- Mapping Protein-Protein Interactions at Birth: Single-Particle Cryo-EM Analysis of a Ribosome-Nascent Globin Complex.ACS central science · 2024Article
- N-glycosylation as a eukaryotic protective mechanism against protein aggregation.Science advances · 2024Article
- Mechanisms and pathology of protein misfolding and aggregation.Nature reviews. Molecular cell biology · 2023Review
- Polymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formation.Nature communications · 2023Article
- HSP70-binding motifs function as protein quality control degrons.Cellular and molecular life sciences : CMLS · 2023Article
- Single residue modulators of amyloid formation in the N-terminal P1-region of α-synuclein.Nature communications · 2022Article
- Modern and prebiotic amino acids support distinct structural profiles in proteins.Open biology · 2022Article
- The effect of mutation on an aggregation-prone protein: An in vivo, in vitro, and in silico analysis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mapping the sequence specificity of heterotypic amyloid interactions enables the identification of aggregation modifiers.Nature communications · 2022Article
- A3D 2.0 Update for the Prediction and Optimization of Protein Solubility.Methods in molecular biology (Clifton, N.J.) · 2022Article
- The cellular modifier MOAG-4/SERF drives amyloid formation through charge complementation.The EMBO journal · 2021Article
- The functions and regulation of heat shock proteins; key orchestrators of proteostasis and the heat shock response.Archives of toxicology · 2021Review
- Cryptic amyloidogenic regions in intrinsically disordered proteins: Function and disease association.Computational and structural biotechnology journal · 2021Article
- Co-Chaperones in Targeting and Delivery of Misfolded Proteins to the 26S Proteasome.Biomolecules · 2020Review
- Behind closed gates - chaperones and charged residues determine protein fate.The EMBO journal · 2020Article
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13 authors at 1 institution in 1 country.
Funding
Abstract
Many chaperones favour binding to hydrophobic sequences that are flanked by basic residues while disfavouring acidic residues. However, the origin of this bias in protein quality control remains poorly understood. Here, we show that while acidic residues are the most efficient aggregation inhibitors, they are also less compatible with globular protein structure than basic amino acids. As a result, while acidic residues allow for chaperone-independent control of aggregation, their use is structurally limited. Conversely, we find that, while being more compatible with globular structure, basic residues are not sufficient to autonomously suppress protein aggregation. Using Hsp70, we show that chaperones with a bias towards basic residues are structurally adapted to prioritize aggregating sequences whose structural context forced the use of the less effective basic residues. The hypothesis that emerges from our analysis is that the bias of many chaperones for basic residues results from fundamental thermodynamic and kinetic constraints of globular structure. This also suggests the co-evolution of basic residues and chaperones allowed for an expansion of structural variety in the protein universe.
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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.