ArticleProceedings of the National Academy of Sciences of the United States of America2012
Cellular crowding imposes global constraints on the chemistry and evolution of proteomes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 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.
The trial behind it
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
99 citing papers in PubMed, 188 citations in OpenAlex.
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- Enzymes in a human cytoplasm model organize into submetabolon complexes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Increased preference for lysine over arginine in spike proteins of SARS-CoV-2 BA.2.86 variant and its daughter lineages.PloS one · 2025Article
- Protein Classes Predicted by Molecular Surface Chemical Features: Machine Learning-Assisted Classification of Cytosol and Secreted Proteins.The journal of physical chemistry. B · 2024Article
- Computational Approaches to Predict Protein-Protein Interactions in Crowded Cellular Environments.Chemical reviews · 2024Review
- Diverging co-translational protein complex assembly pathways are governed by interface energy distribution.Nature communications · 2024Article
- Application of Machine Learning in the Quantitative Analysis of the Surface Characteristics of Highly Abundant Cytoplasmic Proteins: Toward AI-Based Biomimetics.Biomimetics (Basel, Switzerland) · 2024Article
- Computational investigation of missense somatic mutations in cancer and potential links to pH-dependence and proteostasis.PloS one · 2024Article
- Agglomeration: when folded proteins clump together.Biophysical reviews · 2023Review
- An Assessment of Quaternary Structure Functionality in Homomer Protein Complexes.Molecular biology and evolution · 2023Article
- Genes Vary Greatly in Their Propensity for Collateral Fitness Effects of Mutations.Molecular biology and evolution · 2023Article
- Epistasis between promoter activity and coding mutations shapes gene evolvability.Science advances · 2023Article
- Mapping the energy landscape of PROTAC-mediated protein-protein interactions.Computational and structural biotechnology journal · 2023Article
- Review
- Purifying selection enduringly acts on the sequence evolution of highly expressed proteins in Escherichia coli.G3 (Bethesda, Md.) · 2022Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 4 countries.
Funding
Abstract
In living cells, functional protein-protein interactions compete with a much larger number of nonfunctional, or promiscuous, interactions. Several cellular properties contribute to avoiding unwanted protein interactions, including regulation of gene expression, cellular compartmentalization, and high specificity and affinity of functional interactions. Here we investigate whether other mechanisms exist that shape the sequence and structure of proteins to favor their correct assembly into functional protein complexes. To examine this question, we project evolutionary and cellular abundance information onto 397, 196, and 631 proteins of known 3D structure from Escherichia coli, Saccharomyces cerevisiae, and Homo sapiens, respectively. On the basis of amino acid frequencies in interface patches versus the solvent-accessible protein surface, we define a propensity or "stickiness" scale for each of the 20 amino acids. We find that the propensity to interact in a nonspecific manner is inversely correlated with abundance. In other words, high abundance proteins have less sticky surfaces. We also find that stickiness constrains protein evolution, whereby residues in sticky surface patches are more conserved than those found in nonsticky patches. Finally, we find that the constraint imposed by stickiness on protein divergence is proportional to protein abundance, which provides mechanistic insights into the correlation between protein conservation and protein abundance. Overall, the avoidance of nonfunctional interactions significantly influences the physico-chemical and evolutionary properties of proteins. Remarkably, the effects observed are consistently larger in E. coli and S. cerevisiae than in H. sapiens, suggesting that promiscuous protein-protein interactions may be freer to accumulate in the human lineage.
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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.