Electrostatic mis-interactions cause overexpression toxicity of proteins in E. coli

PLoS One. 2013 May 29;8(5):e64893. doi: 10.1371/journal.pone.0064893. Print 2013.

Abstract

A majority of E. coli proteins when overexpressed inhibit its growth, but the reasons behind overexpression toxicity of proteins remain unknown. Understanding the mechanism of overexpression toxicity is important from evolutionary, biotechnological and possibly clinical perspectives. Here we study sequence and functional features of cytosolic proteins of E. coli associated with overexpression toxicity to understand its mechanism. We find that number of positively charged residues is significantly higher in proteins showing overexpression toxicity. Very long proteins also show high overexpression toxicity. Among the functional classes, transcription factors and regulatory proteins are enriched in toxic proteins, while catalytic proteins are depleted. Overexpression toxicity could be predicted with reasonable accuracy using these few properties. The importance of charged residues in overexpression toxicity indicates that nonspecific electrostatic interactions resulting from protein overexpression cause toxicity of these proteins and suggests ways to improve the expression level of native and foreign proteins in E. coli for basic research and biotechnology. These results might also be applicable to other bacterial species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / genetics*
  • Amino Acids / metabolism
  • Escherichia coli / genetics*
  • Escherichia coli / growth & development
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics*
  • Escherichia coli Proteins / metabolism
  • Gene Expression Regulation, Bacterial*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Periplasmic Proteins / chemistry
  • Periplasmic Proteins / genetics
  • Periplasmic Proteins / metabolism
  • Static Electricity
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Amino Acids
  • Escherichia coli Proteins
  • Membrane Proteins
  • Periplasmic Proteins
  • Transcription Factors

Grant support

CSIR (Council for Scientific and Industrial Research) funding through IGIB (Institute of Genomics and Integrative Biology). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.