Functional Amyloid Protection in the Eye Lens: Retention of α-Crystallin Molecular Chaperone Activity after Modification into Amyloid Fibrils.
Functional Amyloid Protection in the Eye Lens: Retention of α-Crystallin Molecular Chaperone Activity after Modification into Amyloid Fibrils.
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DOI：
10.3390/biom7030067
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发表时间：
2017-09-12
期刊：
影响因子：
5.5
通讯作者：
Carver JA
中科院分区：
文献类型：
--
作者：
Garvey M;Ecroyd H;Ray NJ;Gerrard JA;Carver JA
淀粉样蛋白原纤维形成发生于广泛的肽和蛋白质，并且通常与蛋白质功能的丧失和/或毒性功能的获得相关，因为蛋白质的天然结构经历重大改变以形成交叉β折叠阵列。现在已经充分认识到，一些淀粉样蛋白原纤维具有生物学功能，这导致对这些所谓的功能性淀粉样蛋白可能保留天然蛋白质的功能或在采用原纤维结构后获得功能的潜力的兴趣增加。本文研究了眼透镜蛋白α-晶体蛋白（α-crystallin）的分子伴侣能力，以及在热和化学应激条件下形成聚集体结构后，其分子伴侣活性的保持甚至增强能力。我们证明，眼透镜α-晶状体蛋白和α B-晶状体蛋白（也广泛存在于透镜外）在结构变化的条件下（包括形成淀粉样纤维和无定形聚集体后）在很大程度上保留了其分子伴侣活性。该结果可与老化对眼透镜中α-晶状体蛋白的结构和伴侣蛋白功能的影响直接相关，特别是其防止晶状体蛋白聚集的能力，从而防止与白内障形成相关的透镜混浊。
Amyloid fibril formation occurs from a wide range of peptides and proteins and is typically associated with a loss of protein function and/or a gain of toxic function, as the native structure of the protein undergoes major alteration to form a cross β-sheet array. It is now well recognised that some amyloid fibrils have a biological function, which has led to increased interest in the potential that these so-called functional amyloids may either retain the function of the native protein, or gain function upon adopting a fibrillar structure. Herein, we investigate the molecular chaperone ability of α-crystallin, the predominant eye lens protein which is composed of two related subunits αA- and αB-crystallin, and its capacity to retain and even enhance its chaperone activity after forming aggregate structures under conditions of thermal and chemical stress. We demonstrate that both eye lens α-crystallin and αB-crystallin (which is also found extensively outside the lens) retain, to a significant degree, their molecular chaperone activity under conditions of structural change, including after formation into amyloid fibrils and amorphous aggregates. The results can be related directly to the effects of aging on the structure and chaperone function of α-crystallin in the eye lens, particularly its ability to prevent crystallin protein aggregation and hence lens opacification associated with cataract formation.
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影响因子：
3.4
作者：
Augusteyn, Robert C.
通讯作者：
Augusteyn, Robert C.
DOI：
10.1016/j.bbagen.2015.08.014
发表时间：
2016-01
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Clark JI
通讯作者：
Clark JI
影响因子：
1.6
作者：
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通讯作者：
Dobson, CM
影响因子：
9.8
作者：
Fowler DM;Koulov AV;Alory-Jost C;Marks MS;Balch WE;Kelly JW
通讯作者：
Kelly JW
DOI：
10.1016/s0141-8130(98)00017-8
发表时间：
1998-05-01
影响因子：
8.2
作者：
Carver, JA;Lindner, RA
通讯作者：
Lindner, RA