ArticleNature chemical biology2014
Energy landscapes of functional proteins are inherently risky.
Article in Nature chemical biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
49 citing papers in PubMed.
- Optimizing Stability in Dynamic Small-Molecule Binding Proteins.Journal of the American Chemical Society · 2026Article
- Marginal Stability of the YB1 Cold-Shock Domain in Cells Enables Binding of Multiple Nucleic Acids.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- How SecB maintains clients in a translocation competent state.Communications biology · 2025Article
- Membrane Charge Drives the Aggregation of TDP-43 Pathological Fragments.Journal of the American Chemical Society · 2025Article
- Heterogeneous folding landscapes and predetermined breaking points within a protein family.Protein science : a publication of the Protein Society · 2024Article
- A Hydrophobic Core Stabilizes the Residual Structure in the RRM2 Intermediate State of the ALS-linked Protein TDP-43.Journal of molecular biology · 2024Article
- Review
- Frustraevo: a web server to localize and quantify the conservation of local energetic frustration in protein families.Nucleic acids research · 2024Article
- Tracing genetic diversity captures the molecular basis of misfolding disease.Nature communications · 2024Article
- Phylogenetic variations in a novel family of hyperstable apple snail egg proteins: insights into structural stability and functional trends.bioRxiv : the preprint server for biology · 2023Article
- Computed Protein-Protein Enthalpy Signatures as a Tool for Identifying Conformation Sampling Problems.Journal of chemical information and modeling · 2023Article
- Nonspecific Amyloid Aggregation of Chicken Smooth-Muscle Titin: In Vitro Investigations.International journal of molecular sciences · 2023Article
- Article
- Structural and Dynamic Determinants of Molecular Recognition in Bile Acid-Binding Proteins.International journal of molecular sciences · 2022Review
- Protein quality control ofFrontiers in cellular neuroscience · 2022Review
- Class-specific interactions between Sis1 J-domain protein and Hsp70 chaperone potentiate disaggregation of misfolded proteins.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Proteome Folding Problem and Cellular Proteostasis.Journal of molecular biology · 2021Review
- An enzyme-based biosensor for monitoring and engineering protein stability in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- How do Chaperones Bind (Partly) Unfolded Client Proteins?Frontiers in molecular biosciences · 2021Review
- Leveraging Population Genomics for Individualized Correction of the Hallmarks of Alpha-1 Antitrypsin Deficiency.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2020Review
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
Evolutionary pressure for protein function leads to unavoidable sampling of conformational states that are at risk of misfolding and aggregation. The resulting tension between functional requirements and the risk of misfolding and/or aggregation in the evolution of proteins is becoming more and more apparent. One outcome of this tension is sensitivity to mutation, in which only subtle changes in sequence that may be functionally advantageous can tip the delicate balance toward protein aggregation. Similarly, increasing the concentration of aggregation-prone species by reducing the ability to control protein levels or compromising protein folding capacity engenders increased risk of aggregation and disease. In this Perspective, we describe examples that epitomize the tension between protein functional energy landscapes and aggregation risk. Each case illustrates how the energy landscapes for the at-risk proteins are sculpted to enable them to perform their functions and how the risks of aggregation are minimized under cellular conditions using a variety of compensatory mechanisms.
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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.