dorsal/arxiv
View SchemaEnhanced self-attraction of proteins and its evolutionary implications
| Authors | D. B. Lyjatsky, E. I. Shakhnovich |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0603017 |
| URL | https://arxiv.org/abs/q-bio/0603017 |
Abstract
Statistical analysis of protein-protein interactions shows anomalously high frequency of homodimers [Ispolatov, I., et al. (2005) Nucleic Acids Res 33, 3629-35]. Furthermore, recent findings [Wright, C.F., et al. (2005) Nature 438, 878-81] demonstrate that maintaining low sequence identity is a key evolutionary mechanism that inhibits protein aggregation. Here, we study statistical properties of interacting protein-like surfaces and predict the effect of universal, enhanced self-attraction of proteins. The effect originates in the fact that a pattern self-match between two identical, even randomly organized interacting protein surfaces is always stronger compared to the pattern match between two different, promiscuous protein surfaces. This finding implies an increased probability of homodimer selection in the course of early evolution. Our simple model of early evolutionary selection of interacting proteins accurately reproduces the experimental data on homodimer interface aminoacid compositions. In addition, we predict that heterodimers evolved from homodimers with the negative design evolutionary pressure applied against promiscuous homodimer formation. We predict that the anti-homodimer negative design evolutionary signal is conveyed through the enrichment of heterodimeric interfaces in polar residues, and most profoundly in glutamic acid and lysine, which is consistent with experimental findings. We predict therefore that the negative design against homodimers is the
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"abstract": "Statistical analysis of protein-protein interactions shows anomalously high\nfrequency of homodimers [Ispolatov, I., et al. (2005) Nucleic Acids Res 33,\n3629-35]. Furthermore, recent findings [Wright, C.F., et al. (2005) Nature 438,\n878-81] demonstrate that maintaining low sequence identity is a key\nevolutionary mechanism that inhibits protein aggregation. Here, we study\nstatistical properties of interacting protein-like surfaces and predict the\neffect of universal, enhanced self-attraction of proteins. The effect\noriginates in the fact that a pattern self-match between two identical, even\nrandomly organized interacting protein surfaces is always stronger compared to\nthe pattern match between two different, promiscuous protein surfaces. This\nfinding implies an increased probability of homodimer selection in the course\nof early evolution. Our simple model of early evolutionary selection of\ninteracting proteins accurately reproduces the experimental data on homodimer\ninterface aminoacid compositions. In addition, we predict that heterodimers\nevolved from homodimers with the negative design evolutionary pressure applied\nagainst promiscuous homodimer formation. We predict that the anti-homodimer\nnegative design evolutionary signal is conveyed through the enrichment of\nheterodimeric interfaces in polar residues, and most profoundly in glutamic\nacid and lysine, which is consistent with experimental findings. We predict\ntherefore that the negative design against homodimers is the",
"arxiv_id": "q-bio/0603017",
"authors": [
"D. B. Lyjatsky",
"E. I. Shakhnovich"
],
"categories": [
"q-bio.BM",
"q-bio.MN"
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"title": "Enhanced self-attraction of proteins and its evolutionary implications",
"url": "https://arxiv.org/abs/q-bio/0603017"
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