The unexpected role of polyubiquitin chains in the formation of fibrillar aggregates.
The unexpected role of polyubiquitin chains in the formation of fibrillar aggregates.
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DOI：
10.1038/ncomms7116
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发表时间：
2015-01-20
影响因子：
16.6
通讯作者：
Shirakawa, Masahiro
中科院分区：
文献类型：
--
作者：
Morimoto, Daichi;Walinda, Erik;Fukada, Harumi;Sou, Yu-Shin;Kageyama, Shun;Hoshino, Masaru;Fujii, Takashi;Tsuchiya, Hikaru;Saeki, Yasushi;Arita, Kyohei;Ariyoshi, Mariko;Tochio, Hidehito;Iwai, Kazuhiro;Namba, Keiichi;Komatsu, Masaaki;Tanaka, Keiji;Shirakawa, Masahiro
已知泛素是最可溶和最稳定折叠的细胞内蛋白质之一，但它通常存在于与包括神经退行性疾病和癌症在内的各种疾病相关的包涵体中。为了深入了解这种矛盾的行为，我们研究了泛素及其聚合链的物理化学性质，导致聚集体的形成。我们发现泛素链的折叠稳定性出乎意料地随着链长的增加而降低，导致淀粉样原纤维的形成。此外，当在细胞中表达时，与EGFP共价连接的多聚泛素链也根据链长度形成聚集体。值得注意的是，这些聚集体通过自噬选择性降解。我们提出了一种新的模型，其中多聚泛素链的物理和化学不稳定性驱动原纤维的形成，然后作为自噬的起始信号。 泛素是一种稳定的可溶性蛋白质，但它通常存在于神经退行性疾病和癌症的包涵体中。Morimoto等人报道，增加泛素链长度导致淀粉样原纤维的形成，其通过自噬机制降解。
Ubiquitin is known to be one of the most soluble and stably folded intracellular proteins, but it is often found in inclusion bodies associated with various diseases including neurodegenerative disorders and cancer. To gain insight into this contradictory behaviour, we have examined the physicochemical properties of ubiquitin and its polymeric chains that lead to aggregate formation. We find that the folding stability of ubiquitin chains unexpectedly decreases with increasing chain length, resulting in the formation of amyloid-like fibrils. Furthermore, when expressed in cells, polyubiquitin chains covalently linked to EGFP also form aggregates depending on chain length. Notably, these aggregates are selectively degraded by autophagy. We propose a novel model in which the physical and chemical instability of polyubiquitin chains drives the formation of fibrils, which then serve as an initiation signal for autophagy. Ubiquitin is a stable and soluble protein, but it is commonly found in inclusion bodies in neurodegenerative disorders and cancer. Here, Morimoto et al. report that increasing ubiquitin chain length leads to the formation of amyloid-like fibrils, which are degraded by an autophagy mechanism.
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DOI：
10.1073/pnas.0303758100
发表时间：
2003-12-23
影响因子：
11.1
作者：
Fändrich, M;Forge, V;Diekmann, S
通讯作者：
Diekmann, S
影响因子：
64.8
作者：
Lindorff-Larsen, K;Best, RB;Vendruscolo, M
通讯作者：
Vendruscolo, M
影响因子：
14.8
作者：
Fawzi, Nicolas L.;Ying, Jinfa;Torchia, Dennis A.;Clore, G. Marius
通讯作者：
Clore, G. Marius
p62/SQSTM1形成自噬降解的蛋白质聚集体，并对亨廷顿蛋白诱导的细胞死亡具有保护作用。
影响因子：
7.8
作者：
Bjorkoy, Geir;Lamark, Trond;Brech, Andreas;Outzen, Heidi;Perander, Maria;Overvatn, Aud;Stenmark, Harald;Johansen, Terje
通讯作者：
Johansen, Terje
影响因子：
2.9
作者：
Ibarra-Molero, B;Loladze, VV;Sanchez-Ruiz, JM
通讯作者：
Sanchez-Ruiz, JM