Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins.
Widespread aggregation and neurodegenerative diseases are associated with supersaturated proteins.
复制标题
DOI：
10.1016/j.celrep.2013.09.043
复制
发表时间：
2013-11-14
期刊：
影响因子：
8.8
通讯作者：
Vendruscolo M
中科院分区：
文献类型：
--
作者：
Ciryam P;Tartaglia GG;Morimoto RI;Dobson CM;Vendruscolo M
蛋白质溶解度的维持是蛋白质稳态的基本方面，因为聚集与细胞毒性和多种人类疾病相关。然而，许多在序列和结构上不相关的蛋白质可以错误折叠和聚集，并且在压力或老化下的生命系统中可以发生广泛的聚集。在这种情况下，一个关键问题是为什么只有某些蛋白质在体内聚集，而其他蛋白质则不会。我们在这里确定的蛋白质最容易聚集的细胞浓度是高相对于它们的溶解度。这些过饱和蛋白质代表了在应激和衰老过程中参与病理聚集的亚稳态蛋白质组，并且在与神经退行性疾病相关的生化过程中过度表达。因此，当保持固有过饱和蛋白质可溶的能力受到损害时，这种细胞过程变得功能失调。因此，丰度和溶解度的同时分析可以使与神经退行性疾病和衰老相关的多种细胞病理学合理化。
The maintenance of protein solubility is a fundamental aspect of protein homeostasis, as aggregation is associated with cytotoxicity and a variety of human diseases. Numerous proteins unrelated in sequence and structure, however, can misfold and aggregate, and widespread aggregation can occur in living systems under stress or ageing. A crucial question in this context is why only certain proteins aggregate in vivo while others do not. We identify here the proteins most vulnerable to aggregation as those whose cellular concentrations are high relative to their solubilities. These supersaturated proteins represent a metastable sub-proteome involved in pathological aggregation during stress and ageing, and are overrepresented in biochemical processes associated with neurodegenerative disorders. Consequently, such cellular processes become dysfunctional when the ability to keep intrinsically supersaturated proteins soluble is compromised. Thus, the simultaneous analysis of abundance and solubility can rationalize the diverse cellular pathologies linked to neurodegenerative diseases and aging.
登录
查看更多内容
影响因子：
9.8
作者：
David DC;Ollikainen N;Trinidad JC;Cary MP;Burlingame AL;Kenyon C
通讯作者：
Kenyon C
影响因子：
8.8
作者：
Gsponer J;Babu MM
通讯作者：
Babu MM
影响因子：
3.5
作者：
Hutt, Darren M.;Powers, Evan T.;Balch, William E.
通讯作者：
Balch, William E.
DOI：
10.1073/pnas.73.9.3035
发表时间：
1976-01-01
影响因子：
11.1
作者：
HOFRICHTER, J;ROSS, PD;EATON, WA
通讯作者：
EATON, WA
影响因子：
5.6
作者：
Agostini, Federico;Vendruscolo, Michele;Tartaglia, Gian Gaetano
通讯作者：
Tartaglia, Gian Gaetano