期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 109, 期 50, 页码 20461-20466出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1209312109
关键词
promiscuity; protein structure; interaction potential
资金
- Human Frontier Science Project
- Stephen Michnick and Universite de Montreal
- Weizmann Institute of Science
- University of Colorado School of Medicine
- National Cancer Institute Physical Sciences Oncology Center initiative [U54-CA143798]
- Medical Research Council [U105161047]
- MRC [MC_U105161047] Funding Source: UKRI
- Medical Research Council [MC_U105161047] Funding Source: researchfish
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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