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Ribosome-mediated folding of partially unfolded ricin A-chain
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UNSPECIFIED (2000) Ribosome-mediated folding of partially unfolded ricin A-chain. JOURNAL OF BIOLOGICAL CHEMISTRY, 275 (13). pp. 9263-9269. ISSN 0021-9258.
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Abstract
After endocytic uptake by mammalian cells, the cytotoxic protein ricin is transported to the endoplasmic reticulum, whereupon the A-chain must cross the lumenal membrane to reach its ribosomal substrates. It is assumed that membrane traversal is preceded by unfolding of ricin A-chain, followed by refolding in the cytosol to generate the native, biologically active toxin. Here we describe biochemical and biophysical analyses of the unfolding of ricin A-chain and its refolding in vitro. We show that native ricin A-chain is surprisingly unstable at pH 7.0, unfolding non-cooperatively above 37 degrees C to generate a partially unfolded state, This species has conformational properties typical of a molten globule, and cannot be refolded to the native state by manip ulation of the buffer conditions or by the addition of a stem-loop dodecaribonucleotide or deproteinized Escherichia coli ribosomal RNA, both of which are substrates for ricin A-chain. By contrast, in the presence of salt-washed ribosomes, partially unfolded ricin A-chain regains full catalytic activity. The data suggest that the conformational stability of ricin A-chain is ideally poised for translocation from the endoplasmic reticulum, Within the cytosol, ricin A-chain molecules may then refold in the presence of ribosomes, resulting in ribosome depurination and cell death.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QD Chemistry | ||||
Journal or Publication Title: | JOURNAL OF BIOLOGICAL CHEMISTRY | ||||
Publisher: | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | ||||
ISSN: | 0021-9258 | ||||
Official Date: | 31 March 2000 | ||||
Dates: |
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Volume: | 275 | ||||
Number: | 13 | ||||
Number of Pages: | 7 | ||||
Page Range: | pp. 9263-9269 | ||||
Publication Status: | Published |
Data sourced from Thomson Reuters' Web of Knowledge
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