Title |
The unexpected role of polyubiquitin chains in the formation of fibrillar aggregates
|
---|---|
Published in |
Nature Communications, January 2015
|
DOI | 10.1038/ncomms7116 |
Pubmed ID | |
Authors |
Daichi Morimoto, Erik Walinda, Harumi Fukada, Yu-Shin Sou, Shun Kageyama, Masaru Hoshino, Takashi Fujii, Hikaru Tsuchiya, Yasushi Saeki, Kyohei Arita, Mariko Ariyoshi, Hidehito Tochio, Kazuhiro Iwai, Keiichi Namba, Masaaki Komatsu, Keiji Tanaka, Masahiro Shirakawa |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 2 | 22% |
Japan | 2 | 22% |
Sweden | 1 | 11% |
Unknown | 4 | 44% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 9 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
India | 1 | <1% |
United States | 1 | <1% |
Unknown | 135 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 37 | 27% |
Researcher | 24 | 17% |
Student > Bachelor | 13 | 9% |
Student > Master | 13 | 9% |
Student > Doctoral Student | 8 | 6% |
Other | 23 | 17% |
Unknown | 20 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 44 | 32% |
Biochemistry, Genetics and Molecular Biology | 39 | 28% |
Chemistry | 17 | 12% |
Immunology and Microbiology | 4 | 3% |
Medicine and Dentistry | 4 | 3% |
Other | 7 | 5% |
Unknown | 23 | 17% |