ArticleJournal of molecular biology2019
Protein Abundance Biases the Amino Acid Composition of Disordered Regions to Minimize Non-functional Interactions.
Article in Journal of molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 40 citations in OpenAlex.
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- Molecular and environmental determinants of biomolecular condensate formation.Nature chemical biology · 2022Review
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- Physics-driven coarse-grained model for biomolecular phase separation with near-quantitative accuracy.Nature computational science · 2021Article
- The Distinct Properties of the Consecutive Disordered Regions Inside or Outside Protein Domains and Their Functional Significance.International journal of molecular sciences · 2021Article
- On the specificity of protein-protein interactions in the context of disorder.The Biochemical journal · 2021Review
- Integration of Data from Liquid-Liquid Phase Separation Databases Highlights Concentration and Dosage Sensitivity of LLPS Drivers.International journal of molecular sciences · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In eukaryotes, disordered regions cover up to 50% of proteomes and mediate fundamental cellular processes. In contrast to globular domains, where about half of the amino acids are buried in the protein interior, disordered regions show higher solvent accessibility, which makes them prone to engage in non-functional interactions. Such interactions are exacerbated by the law of mass action, prompting the question of how they are minimized in abundant proteins. We find that interaction propensity or "stickiness" of disordered regions negatively correlates with their cellular abundance, both in yeast and human. Strikingly, considering yeast proteins where a large fraction of the sequence is disordered, the correlation between stickiness and abundance reaches R=-0.55. Beyond this global amino-acid composition bias, we identify three rules by which amino-acid composition of disordered regions adjusts with high abundance. First, lysines are preferred over arginines, consistent with the latter amino acid being stickier than the former. Second, compensatory effects exist, whereby a sticky region can be tolerated if it is compensated by a distal non-sticky region. Third, such compensation requires a lower average stickiness at the same abundance when compared to a scenario where stickiness is homogeneous throughout the sequence. We validate these rules experimentally, employing them as different strategies to rescue an otherwise sticky protein fragment from aggregation. Our results highlight that non-functional interactions represent a significant constraint in cellular systems and reveal simple rules by which protein sequences adapt to that constraint. Data from this work are deposited in Figshare, at https://doi.org/10.6084/m9.figshare.8068937.v3.
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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.