Large-scale experimental studies show unexpected amino acid effects on protein expression and solubility in vivo in E. coli.

Microbial Informatics and Experimentation
W Nicholson PriceJohn F Hunt

Abstract

The biochemical and physical factors controlling protein expression level and solubility in vivo remain incompletely characterized. To gain insight into the primary sequence features influencing these outcomes, we performed statistical analyses of results from the high-throughput protein-production pipeline of the Northeast Structural Genomics Consortium. Proteins expressed in E. coli and consistently purified were scored independently for expression and solubility levels. These parameters nonetheless show a very strong positive correlation. We used logistic regressions to determine whether they are systematically influenced by fractional amino acid composition or several bulk sequence parameters including hydrophobicity, sidechain entropy, electrostatic charge, and predicted backbone disorder. Decreasing hydrophobicity correlates with higher expression and solubility levels, but this correlation apparently derives solely from the beneficial effect of three charged amino acids, at least for bacterial proteins. In fact, the three most hydrophobic residues showed very different correlations with solubility level. Leu showed the strongest negative correlation among amino acids, while Ile showed a slightly positive correlation in ...Continue Reading

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Citations

Sep 24, 2013·Journal of Structural and Functional Genomics·William H EschenfeldtAndrzej Joachimiak
Aug 4, 2015·Colloids and Surfaces. B, Biointerfaces·Diana Fusco, Patrick Charbonneau
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May 4, 2016·Acta Crystallographica. Section D, Structural Biology·Andrew J TebbenSteven Sheriff
Jan 9, 2021·Bioinformatics·Jiri HonJiri Damborsky

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Methods Mentioned

BETA
gel-filtration
X-ray
NMR
protein folding
static light-scattering

Software Mentioned

PhD
BIOMT
ExPASy
DISOPRED2
NESG
PROF
STATA
TargetDB
TMMHMM

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