Save Sight Institute, Sydney Eye Hospital, University of Sydney, Sydney, New South Wales 2000, Australia.
Protein Sci. 2012 Jul;21(7):1074-9. doi: 10.1002/pro.2095. Epub 2012 Jun 11.
Human aging is associated with the deterioration of long-lived proteins. Gradual cumulative modifications to the life-long proteins of the lens may ultimately be responsible for the pronounced alterations to the optical and physical properties that characterize lenses from older people. γS crystallin, a major human lens protein, is known to undergo several age-dependent changes. Using proteomic techniques, a site of deamidation involving glutamine 92 has been characterized and its time course established. The proportion of deamidation increased from birth to teen-age years and then plateaud. Deamidation at this site increased again in the eighth decade of life. There was no significant difference in the extent of deamidation between cataract and age-matched normal lenses. Gln92 is located in the linker region between the two domains, and the introduction of a negative charge at this site may alter the interaction between the two regions of the protein. Gln170, which is located in another unstructured part of γS crystallin, showed a similar deamidation profile to that of Gln92. As the other Gln residues in β-sheet regions of γS crystallin appear to remain as amides, modification of Gln92 and Gln170 thus conforms to a pattern whereby deamidation is localized to the unstructured regions of long-lived proteins.
人类衰老与长寿蛋白的恶化有关。晶状体中终身蛋白质的逐渐累积变化最终可能是导致老年人晶状体光学和物理性质明显改变的原因。γS 晶体蛋白是一种主要的人类晶状体蛋白，已知其会发生几种年龄依赖性变化。使用蛋白质组学技术，已经确定了涉及谷氨酰胺 92 的脱酰胺化部位，并确定了其时间过程。从出生到青少年时期，脱酰胺化的比例增加，然后达到平台期。在生命的第八个十年中，该部位的脱酰胺化再次增加。白内障和年龄匹配的正常晶状体之间的脱酰胺化程度没有显著差异。Gln92 位于两个结构域之间的连接区，该部位的负电荷引入可能会改变蛋白质的两个区域之间的相互作用。Gln170 位于 γS 晶体蛋白另一个无规卷曲区，其脱酰胺化模式与 Gln92 相似。由于 γS 晶体蛋白 β 折叠区的其他 Gln 残基似乎仍然是酰胺，因此 Gln92 和 Gln170 的修饰符合脱酰胺化定位于长寿蛋白无规卷曲区的模式。
