Evans, P. and Wyatt, K. and Wistow, G.J. and Bateman, O.A. and Wallace, Bonnie A. and Slingsby, Christine (2004) The P23T cataract mutation causes loss of solubility of folded γD-crystallin. Journal of Molecular Biology 343 (2), pp. 435-444. ISSN 0022-2836.
Abstract
Mutations in the human γD-crystallin gene have been linked to several types of congenital cataracts. In particular, the Pro23 to Thr (P23T) mutation of human γD crystallin has been linked to cerulean, lamellar, coralliform, and fasciculiform congenital cataracts. We have expressed and purified wild-type human γD, P23T, and the Pro23 to Ser23 (P23S) mutant. Our measurements show that P23T is significantly less soluble than wild-type human γD, with P23S having an intermediate solubility. Using synchrotron radiation circular dichroism spectroscopy, we have determined that the P23T mutant has a slightly increased content of β-sheet, which may be attributed to the extension of an edge β-strand due to the substitution of Pro23 with a residue able to form hydrogen bonds. Neither of the point mutations appears to have reduced the thermal stability of the protein significantly, nor its resistance to guanidine hydrochloride-induced unfolding. These results suggest that insolubility, rather than loss of stability, is the primary basis for P23T congenital cataracts.
Metadata
| Item Type: | Article |
|---|---|
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Depositing User: | Sarah Hall |
| Date Deposited: | 21 May 2019 11:37 |
| Last Modified: | 02 Aug 2023 17:51 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/27611 |
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