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PN Farnsworth, PH Frederikse, K Singh; The Role of Alpha-crystallin in Fiber Cell Dehydration . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3555.
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Purpose:To investigate the structural and functional significance of the self-complementary motifs (SCM) in α-crystallin subunits, αA and αB. Methods: Several computational biochemical programs such as Sybyl for molecular modeling and GCG for sequence comparisons were used to identify other proteins with SCM and to correlate their structure/function relationship with α-crystallin subunits. These data were also corrrelated with published and new experimental results. Results: SCM within insulin (B21-29) and Aß (14-23) share both homology and ß sheet secondary structure with the SCM1 of the more lens specific αA (Farnsworth and Singh, 2000}. Interaction of the SCM in reverse order of Aß and insulin form pseudo ß sheets required for the nucleation of amyloid protein structure. This plus the stacking of true ß sheets form the core of amyloid structure. The pseudo ß sheets provide the binding sites for the amyloid stains, Congo red and thioflavin T. α-Crystallin also binds these stains.The formation of amyloid structure is accompanied by the rapid extrusion of water and significant protein dehydration. Conclusion: These observations provide a chemical and physiological basis for the lens fiber cell dehydration that occurs precisely where amyloid staining begins in cortical fibers (Frederikse, 2000). This also correlates with a precipitous increase in protein concentration and an altered crystallin supramolecular order, our proposed protein phase transition zone (Gagna et al., 1997). The stability and the resistance to perturbation by denaturants and proteolysis of amyloid-like dehydrated ß sheet structure may contribute to the long term maintenance of lens transparency.
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