Direct proteolysis-based purification of an overexpressed hyperthermophile protein from Escherichia coli lysate: a novel exploitation of the link between structural stability and proteolytic resistance.
DIR@IMTECH: CSIR-Institute of Microbial Technology
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Title |
Direct proteolysis-based purification of an overexpressed hyperthermophile protein from Escherichia coli lysate: a novel exploitation of the link between structural stability and proteolytic resistance.
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Creator |
Mukherjee, Sourav
Guptasarma, Purnananda |
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Subject |
QR Microbiology
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Description |
The susceptibility of a peptide bond to cleavage by a protease is determined by: (a) the flexibility of the protein chain region in which it is located, (b) the extent to which the bond is exposed, and (c) the nature of the local interactions made by the sidechains of its flanking residues. Each of these parameters is known to be influenced by the overall structural stability of the protein; thus, proteins of higher structurally stability commonly show higher resistance to proteolysis. Extrapolating this relationship to 'ultrastable' proteins, our intention here was to investigate whether a hyperthermophile protein expressed and folded within Escherichia coli could prove to be so resistant to proteolysis as to allow direct purification from complex mixtures of E. coli cytoplasmic and/or membrane proteins, through proteolytic means. Thus, we cloned the gene encoding the triosephosphate isomerase enzyme of Pyrococcus furiosus (PfuTIM) and overexpressed it in E. coli in fusion with glutathione S-transferase (GST). The GST-PfuTIM fusion product partitioned mainly into the insoluble fraction of the whole cell lysate. Upon exposure of the E. coli cell lysate precipitate fractions to the non-specific protease, subtilisin, all polypeptides barring PfuTIM (including the GST affinity tag cloned in fusion with PfuTIM) were found to be degraded to undetectable levels. Trace residual amounts of an E. coli protein, OmpF, survived proteolytic digestion, together with an extremely pure population of PfuTIM. Either autonomously or in combination with the more conventional method of heating solutions to enrich heat-stable proteins through the thermal unfolding and aggregation of all other proteins, such proteolysis-based purification could prove to be useful.
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Publisher |
Elsevier Science
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Date |
2005-03
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://crdd.osdd.net/open/187/1/guptasarma2004.2.pdf
Mukherjee, Sourav and Guptasarma, Purnananda (2005) Direct proteolysis-based purification of an overexpressed hyperthermophile protein from Escherichia coli lysate: a novel exploitation of the link between structural stability and proteolytic resistance. Protein expression and purification, 40 (1). pp. 71-6. ISSN 1046-5928 |
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Relation |
http://www.sciencedirect.com/science/article/pii/S1046592804003973
http://crdd.osdd.net/open/187/ |
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