Bimodal protein solubility distribution revealed by an aggregation analysis of the entire ensemble of Escherichia coli proteins

Tatsuya Niwa, Bei Wen Ying, Katsuyo Saito, Wenzhen Jin, Shoji Takada, Takuya Ueda, Hideki Taguchi

Research output: Contribution to journalArticle

142 Citations (Scopus)

Abstract

Protein folding often competes with intermolecular aggregation, which in most cases irreversibly impairs protein function, as exemplified by the formation of inclusion bodies. Although it has been empirically determined that some proteins tend to aggregate, the relationship between the protein aggregation propensities and the primary sequences remains poorly understood. Here, we individually synthesized the entire ensemble of Escherichia coli proteins by using an in vitro reconstituted translation system and analyzed the aggregation propensities. Because the reconstituted translation system is chaperone-free, we could evaluate the inherent aggregation propensities of thousands of proteins in a translation-coupled manner. A histogram of the solubilities, based on data from 3,173 translated proteins, revealed a clear bimodal distribution, indicating that the aggregation propensities are not evenly distributed across a continuum. Instead, the proteins can be categorized into 2 groups, soluble and aggregation-prone proteins. The aggregation propensity is most prominently correlated with the structural classification of proteins, implying that the prediction of aggregation propensity requires structural information about the protein.

Original languageEnglish
Pages (from-to)4201-4206
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number11
DOIs
Publication statusPublished - 2009 Mar 17

Keywords

  • Cell-free translation
  • Protein aggregation
  • Protein folding

ASJC Scopus subject areas

  • General

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