| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-91 |
Sentence |
denotes |
Site-specific Interaction Mapping of Phosphorylated Ubiquitin to Uncover Parkin Activation. |
| T2 |
92-156 |
Sentence |
denotes |
Damaged mitochondria are eliminated through autophagy machinery. |
| T3 |
157-276 |
Sentence |
denotes |
A cytosolic E3 ubiquitin ligase Parkin, a gene product mutated in familial Parkinsonism, is essential for this pathway. |
| T4 |
277-457 |
Sentence |
denotes |
Recent progress has revealed that phosphorylation of both Parkin and ubiquitin at Ser(65) by PINK1 are crucial for activation and recruitment of Parkin to the damaged mitochondria. |
| T5 |
458-610 |
Sentence |
denotes |
However, the mechanism by which phosphorylated ubiquitin associates with and activates phosphorylated Parkin E3 ligase activity remains largely unknown. |
| T6 |
611-785 |
Sentence |
denotes |
Here, we analyze interactions between phosphorylated forms of both Parkin and ubiquitin at a spatial resolution of the amino acid residue by site-specific photo-crosslinking. |
| T7 |
786-940 |
Sentence |
denotes |
We reveal that the in-between-RING (IBR) domain along with RING1 domain of Parkin preferentially binds to ubiquitin in a phosphorylation-dependent manner. |
| T8 |
941-1185 |
Sentence |
denotes |
Furthermore, another approach, the Fluoppi (fluorescent-based technology detecting protein-protein interaction) assay, also showed that pathogenic mutations in these domains blocked interactions with phosphomimetic ubiquitin in mammalian cells. |
| T9 |
1186-1473 |
Sentence |
denotes |
Molecular modeling based on the site-specific photo-crosslinking interaction map combined with mass spectrometry strongly suggests that a novel binding mechanism between Parkin and ubiquitin leads to a Parkin conformational change with subsequent activation of Parkin E3 ligase activity. |
