title: Electrostatic mis-interactions cause overexpression toxicity of proteins in E. coli.
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.
authors.affiliation: G. N. Ramachandran Knowledge Center for Genome Informatics, Institute of Genomics and Integrative Biology (Council of Scientific and Industrial Research), Delhi, India. gajinder.pal.singh@gmail.com
authors.forename: Gajinder Pal
authors.initials: GP
authors.lastname: Singh
authors.forename: Debasis
authors.initials: D
authors.lastname: Dash
mesh_terms: D000596:Amino Acids / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D033903:Periplasmic Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D055672:Static Electricity; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000596:Amino Acids; D029968:Escherichia coli Proteins; D008565:Membrane Proteins; D033903:Periplasmic Proteins; D014157:Transcription Factors