| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-90 |
Sentence |
denotes |
Enhanced molecular mobility of ordinarily structured regions drives polyglutamine disease. |
| T2 |
91-234 |
Sentence |
denotes |
Polyglutamine expansion is a hallmark of nine neurodegenerative diseases, with protein aggregation intrinsically linked to disease progression. |
| T3 |
235-369 |
Sentence |
denotes |
Although polyglutamine expansion accelerates protein aggregation, the misfolding process is frequently instigated by flanking domains. |
| T4 |
370-492 |
Sentence |
denotes |
For example, polyglutamine expansion in ataxin-3 allosterically triggers the aggregation of the catalytic Josephin domain. |
| T5 |
493-593 |
Sentence |
denotes |
The molecular mechanism that underpins this allosteric aggregation trigger remains to be determined. |
| T6 |
594-746 |
Sentence |
denotes |
Here, we establish that polyglutamine expansion increases the molecular mobility of two juxtaposed helices critical to ataxin-3 deubiquitinase activity. |
| T7 |
747-897 |
Sentence |
denotes |
Within one of these helices, we identified a highly amyloidogenic sequence motif that instigates aggregation and forms the core of the growing fibril. |
| T8 |
898-1026 |
Sentence |
denotes |
Critically, by mutating residues within this key region, we decrease local structural fluctuations to slow ataxin-3 aggregation. |
| T9 |
1027-1259 |
Sentence |
denotes |
This provides significant insight, down to the molecular level, into how polyglutamine expansion drives aggregation and explains the positive correlation between polyglutamine tract length, protein aggregation, and disease severity. |
