Expression of Active Streptolysin O in Escherichia coli as a Maltose-Binding-Protein-Streptolysin-O Fusion Protein. The N-Terminal 70 Amino Acids are not Required for Hemolytic Activity
DIR@IMTECH: CSIR-Institute of Microbial Technology
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Title |
Expression of Active Streptolysin O in Escherichia coli as a Maltose-Binding-Protein-Streptolysin-O Fusion Protein. The N-Terminal 70 Amino Acids are not Required for Hemolytic Activity
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Creator |
Weller, Ulrich
Muller, Lutz Messner, Martina Palmer, Michael Valeva, Angela Tranum-Jensen, Jorgen Agrawal, Pushpa Biermann, Christine Dobereiner, Andreas Kehoe, Michael A. Bhakdi, Sucharit |
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Subject |
QD Chemistry
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Description |
Streptolysin O (SLO) is the prototype of a family of cytolysins that consists of proteins which bind to cholesterol and form very large transmembrane pores. Structure/function studies on the pore-forming cytolysin SLO have been complicated by the proteolytic inactivation of a substantial portion of recombinant SLO (rSLO) expressed in Escherichia coli. To overcome this problem, translational fusions between the E. coli maltose-binding protein (MBP) gene and SLO were constructed, using the vectors pMAL-p2 and pMAL-c2. MBP-SLO fusion proteins were degraded if secreted into the E. coli periplasm, but intact, soluble MBP-SLO fusion proteins were produced at high levels in the cytoplasm. Active SLO with the expected N-terminus was separated from the MBP carrier by cleavage with factor Xa. Cleavage with plasmin or trypsin also yielded active, but slightly smaller forms of SLO. Surprisingly, uncleaved MBP-SLO was also hemolytic and cytotoxic to human fibroblasts and keratinocytes. The MBP-SLO fusion protein displayed equal activities to SLO. Sucrose density gradient analyses showed that the fusion protein assembled into polymers, and no difference in structure was discerned compared with polymers formed by native SLO. These studies show that the N-terminal 70 residues of mature (secreted) SLO are not required for pore formation and that the N-terminus of the molecule is probably not inserted into the bilayer. In addition, they provide a simple means for producing mutants for structure/function studies and highly purified SLO for use as a permeabilising reagent in cell biology research.
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Publisher |
Wiley
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Date |
1996
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://crdd.osdd.net/open/725/1/agrawal1996.pdf
Weller, Ulrich and Muller, Lutz and Messner, Martina and Palmer, Michael and Valeva, Angela and Tranum-Jensen, Jorgen and Agrawal, Pushpa and Biermann, Christine and Dobereiner, Andreas and Kehoe, Michael A. and Bhakdi, Sucharit (1996) Expression of Active Streptolysin O in Escherichia coli as a Maltose-Binding-Protein-Streptolysin-O Fusion Protein. The N-Terminal 70 Amino Acids are not Required for Hemolytic Activity. European Journal of Biochemistry, 236 (1). pp. 34-39. ISSN 0014-2956 |
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Relation |
http://dx.doi.org/10.1111/j.1432-1033.1996.00034.x
http://crdd.osdd.net/open/725/ |
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