Abstract
The ionic liquid N-ethyl-N′-methyl imidazolium chloride (EMIMCl) has been described as being very efficient in promoting refolding of the recombinant plasminogen activator rPA. Our study reveals that molar concentrations of EMIMCl increase the solubility of native and unfolded proteins due to favorable interactions with amino acid side chains rather than favorably interacting with the peptide backbone. This delicate balance of favorable interactions with side chains and unfavorable interactions with the peptide backbone provides a molecular explanation of how EMIMCl suppresses protein aggregation and simultaneously promotes refolding. By contrast, high concentrations of EMIMCl denature proteins because of a reduced water content and strong favorable interactions with amino acid side chains. This denatured species is not soluble and aggregates because, in contrast to the classical denaturants, guanidine hydrochloride and urea, EMIMCl does not solubilize the peptide backbone. Structured digital abstract PNP and PNP bind by molecular sieving (1, 2, 3, 4) The ionic liquid EMIMCl is efficient in promoting the refolding of rPA. Molar concentrations of EMIMCl increase the solubility of native and unfolded proteins due to favorable interactions with amino acid side chains, while the interaction with the peptide backbone is unfavorable. Although a refolding enhancer on one side, high concentrations of EMIMCl result in denaturation and aggregation of proteins.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1738-1749 |
| Number of pages | 12 |
| Journal | FEBS Journal |
| Volume | 281 |
| Issue number | 7 |
| DOIs | |
| State | Published - 2014 |
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Keywords
- aggregation
- CM-rPA
- EMIMCl
- protein solubility
- tc-rPA
ASJC Scopus subject areas
- Biochemistry
- Cell Biology
- Molecular Biology
Cite this
The effects of N-ethyl-N′-methyl imidazolium chloride on the solubility, stability and aggregation of tc-rPA. / Tischer, Alexander; Pultke, Heiko; Topf, Andrea; Auton, Matthew T; Lange, Christian; Lilie, Hauke.
In: FEBS Journal, Vol. 281, No. 7, 2014, p. 1738-1749.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The effects of N-ethyl-N′-methyl imidazolium chloride on the solubility, stability and aggregation of tc-rPA
AU - Tischer, Alexander
AU - Pultke, Heiko
AU - Topf, Andrea
AU - Auton, Matthew T
AU - Lange, Christian
AU - Lilie, Hauke
PY - 2014
Y1 - 2014
N2 - The ionic liquid N-ethyl-N′-methyl imidazolium chloride (EMIMCl) has been described as being very efficient in promoting refolding of the recombinant plasminogen activator rPA. Our study reveals that molar concentrations of EMIMCl increase the solubility of native and unfolded proteins due to favorable interactions with amino acid side chains rather than favorably interacting with the peptide backbone. This delicate balance of favorable interactions with side chains and unfavorable interactions with the peptide backbone provides a molecular explanation of how EMIMCl suppresses protein aggregation and simultaneously promotes refolding. By contrast, high concentrations of EMIMCl denature proteins because of a reduced water content and strong favorable interactions with amino acid side chains. This denatured species is not soluble and aggregates because, in contrast to the classical denaturants, guanidine hydrochloride and urea, EMIMCl does not solubilize the peptide backbone. Structured digital abstract PNP and PNP bind by molecular sieving (1, 2, 3, 4) The ionic liquid EMIMCl is efficient in promoting the refolding of rPA. Molar concentrations of EMIMCl increase the solubility of native and unfolded proteins due to favorable interactions with amino acid side chains, while the interaction with the peptide backbone is unfavorable. Although a refolding enhancer on one side, high concentrations of EMIMCl result in denaturation and aggregation of proteins.
AB - The ionic liquid N-ethyl-N′-methyl imidazolium chloride (EMIMCl) has been described as being very efficient in promoting refolding of the recombinant plasminogen activator rPA. Our study reveals that molar concentrations of EMIMCl increase the solubility of native and unfolded proteins due to favorable interactions with amino acid side chains rather than favorably interacting with the peptide backbone. This delicate balance of favorable interactions with side chains and unfavorable interactions with the peptide backbone provides a molecular explanation of how EMIMCl suppresses protein aggregation and simultaneously promotes refolding. By contrast, high concentrations of EMIMCl denature proteins because of a reduced water content and strong favorable interactions with amino acid side chains. This denatured species is not soluble and aggregates because, in contrast to the classical denaturants, guanidine hydrochloride and urea, EMIMCl does not solubilize the peptide backbone. Structured digital abstract PNP and PNP bind by molecular sieving (1, 2, 3, 4) The ionic liquid EMIMCl is efficient in promoting the refolding of rPA. Molar concentrations of EMIMCl increase the solubility of native and unfolded proteins due to favorable interactions with amino acid side chains, while the interaction with the peptide backbone is unfavorable. Although a refolding enhancer on one side, high concentrations of EMIMCl result in denaturation and aggregation of proteins.
KW - aggregation
KW - CM-rPA
KW - EMIMCl
KW - protein solubility
KW - tc-rPA
UR - http://www.scopus.com/inward/record.url?scp=84897490190&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84897490190&partnerID=8YFLogxK
U2 - 10.1111/febs.12736
DO - 10.1111/febs.12736
M3 - Article
C2 - 24506586
AN - SCOPUS:84897490190
VL - 281
SP - 1738
EP - 1749
JO - FEBS Journal
JF - FEBS Journal
SN - 1742-464X
IS - 7
ER -