Purkiss, Andrew G. and Bateman, Orval A. and Wyatt, K. and Wilmarth, P.A. and David, L.L. and Wistow, G.J. and Slingsby, Christine (2007) Biophysical properties of [gamma]C-Crystallin in human and mouse eye lens: the role of molecular dipoles. Journal of Molecular Biology 372 (1), 205 - 222. ISSN 0022-2836.
Abstract
The eye lens is packed with soluble crystallin proteins, providing a lifetime of transparency and light refraction. γ-Crystallins are major components of the dense, high refractive index central regions of the lens and generally have high solubility, high stability and high levels of cysteine residues. Human γC belongs to a group of γ-crystallins with a pair of cysteine residues at positions 78 and 79. Unlike other γ-crystallins it has relatively low solubility, whereas mouse γC, which has the exposed C79 replaced with arginine, and a novel mouse splice variant, γCins, are both highly soluble. Furthermore, human γC is extremely stable, while the mouse orthologs are less stable. Evolutionary pressure may have favoured stability over solubility for human γC and the reverse for the orthologs in the mouse. Mutation of C79 to R79, in human γC, greatly increased solubility, however, neither form produced crystals. Remarkably, when the human γD R36S crystallization cataract mutation was mimicked in human γC-crystallin, the solubility of γC was dramatically increased, although it still did not crystallize. The highly soluble mouse γC-crystallin did crystallize. Its X-ray structure was solved and used in homology modelling of human γC, and its mutants C79R and R36S. The human γD R36S mutant was also modelled from human γD coordinates. Molecular dynamics simulation of the six molecules in the solution state showed that the human γCs differed from γDs in domain pairing, behaviour that correlates with interface sequence changes. When the fluctuations of the calculated molecular dipoles, for the six structures, over time were analysed, characteristic patterns for soluble γC and γD proteins were observed. Individual sequence changes that increase or decrease solubility correlated well with changes in the magnitude and direction of these dipoles. It is suggested that changes in surface residues have allowed adaptation for the differing needs of human and mouse lenses.
Metadata
| Item Type: | Article |
|---|---|
| Keyword(s) / Subject(s): | crystallin, cysteine, eye lens, protein solubility, solution interactions |
| School: | Birkbeck Faculties and Schools > Faculty of Science > School of Natural Sciences |
| Research Centres and Institutes: | Structural Molecular Biology, Institute of (ISMB) |
| Depositing User: | Administrator |
| Date Deposited: | 09 Aug 2011 09:30 |
| Last Modified: | 02 Aug 2023 16:55 |
| URI: | https://eprints.bbk.ac.uk/id/eprint/3959 |
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