Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5704023 | Experimental Eye Research | 2017 | 28 Pages |
Abstract
Deamidation of Glu147 in human αA-crystallin is common in aged cataractous lenses (Hains and Truscott, Invest. Ophthalmol. Vis. Sci. 2010, 51, 3107). Accordingly, this modification may have a causative effect in cataract. αA-crystallin is a small heat-shock molecular chaperone protein that prevents aggregation of proteins and is the principal defence against crystallin unfolding and aggregation in the ageing lens. Deamidated Q147E αA-crystallin was structurally characterised using a variety of spectroscopic and biophysical methods, including NMR, circular dichroism and fluorescence spectroscopy and dynamic light scattering. The effect of Glu147 deamidation on αA-crystallin in vitro chaperone ability was determined for a variety of aggregating proteins. Compared to the wild type protein, Q147E αA-crystallin generally exhibited slightly reduced chaperone ability and a small loss of overall structure in its central α-crystallin domain while also showing significantly enhanced thermal stability and a tendency to form slightly larger oligomers. As αA-crystallin is the major lens protein, even a small loss of function could combine with other sources of age-related damage to the crystallins to contribute to lens opacification.
Keywords
RCMreduced and carboxymethylatedαA-CrystallinsHSPDEAENOESYTOCSYHSQCADHDTTNuclear Overhauser Effect SpectroscopYαB-crystallinCataractpost-translational modificationAlcohol dehydrogenaseDeamidationThTThioflavin TdithiothreitolAgeingTotal correlation spectroscopyMALSwild typemulti-angle light scatteringSmall heat-shock proteinheteronuclear single quantum coherence
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Authors
Nicholas J. Ray, Damien Hall, John A. Carver,