Identification of residual structure within denatured antichymotrypsin: implications for serpin folding and misfolding
Pearce, Mary C., Cabrita, Lisa D., Rubin, Harvey, Gore, Michael G. and Bottomley, Stephen P. (2004) Identification of residual structure within denatured antichymotrypsin: implications for serpin folding and misfolding. Biochemical and Biophysical Research Communications, 324, (2), 729-735. (doi:10.1016/j.bbrc.2004.09.105).
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Description/Abstract
The native serpin fold is metastable and possesses the inherent ability to convert into more stable, but inactive, conformations. In order to understand why serpins attain the native fold instead of other more thermodynamically favourable folds we have investigated the presence of residual structure within denatured antichymotrypsin (ACT). Through mutagenesis we created a single tryptophan variant of ACT in which a Trp residue (276) is situated on the H-helix, located within a region known as the B/C barrel. The presence of residual structure around Trp 276 in 5 M guanidine hydrochloride (GdnHCl) was shown by fluorescence and circular dichroism spectroscopy and fluorescence lifetime experiments. The residual structure was disrupted in the presence of 5 M guanidine thiocyanate (GdnSCN). Protein refolding studies showed that significant refolding could be achieved from the GdnHCl denatured state but not the GdnSCN denatured form. The implications of these data on the folding and misfolding of the serpin superfamily are discussed.
| Item Type: | Article |
|---|---|
| ISSNs: | 0006-291X (print) |
| Related URLs: | |
| Keywords: | serpin, conformational disease, protein misfolding, residual structure, aggregation, antichymotrypsin, antitrypsin, protein folding |
| Subjects: | Q Science > QH Natural history > QH301 Biology |
| Divisions: | University Structure - Pre August 2011 > School of Biological Sciences |
| Item ID: | 56509 |
| Date Deposited: | 07 Aug 2008 |
| Last Modified: | 12 May 2013 01:15 |
| Contributors: | Pearce, Mary C. (Author) Cabrita, Lisa D. (Author) Rubin, Harvey (Author) Gore, Michael G. (Author) Bottomley, Stephen P. (Author) |
| Date: | 12 November 2004 |
| Status: | Published |
| URI: | http://eprints.soton.ac.uk/id/eprint/56509 |
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