Selectivity of Lewy body protein interactions along the aggregation pathway of α-synuclein.
Selectivity of Lewy body protein interactions along the aggregation pathway of α-synuclein.
复制标题
α-突触核蛋白聚集途径上路易体蛋白相互作用的选择性。
DOI：
10.1038/s42003-021-02624-x
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发表时间：
2021-09-23
影响因子：
5.9
通讯作者：
Sierecki E
中科院分区：
文献类型：
--
作者：
Leitão ADG;Rudolffi-Soto P;Chappard A;Bhumkar A;Lau D;Hunter DJB;Gambin Y;Sierecki E
α-突触核蛋白（α-SYN）的聚集遵循低聚物、原纤维和原纤维形式的级联反应，最终形成路易体（LB），这是帕金森病的病理标志。虽然LB含有超过70种蛋白质，但α-SYN聚集途径的相互作用潜力尚不清楚。在这里，我们提出了65种蛋白与不同种类α-SYN相互作用的图谱。我们使用AlphaScreen（一种用于检测蛋白质相互作用的灵敏纳米珠发光试验）来测量与单体α-SYN的结合。我们使用α-SYN的病理突变体（A30P， G51D和A53T）来获取寡聚物物种，它们形成具有不同性质的寡聚物。最后，我们从重组α-SYN中生成淀粉样蛋白原纤维。在单分子光谱装置上，用双色重合检测（TCCD）测量了与低聚物和原纤维的结合。总之，我们证明LB成分被募集到α-SYN聚集的特定步骤中，揭示了未来在突触核蛋白病中调节聚集的目标。为了更好地理解导致α-突触核蛋白（野生型和突变型）病理聚集的蛋白质相互作用的特定级联，leit<e:1>等人提出了一种方法来测量α-突触的单体、低聚体和纤维状形式与65种蛋白质的相互作用，这些蛋白质先前被证明是路易小体的组成部分。这种方法有助于理解导致α-syn聚集的蛋白质结合事件的序列。
The aggregation of alpha-synuclein (α-SYN) follows a cascade of oligomeric, prefibrillar and fibrillar forms, culminating in the formation of Lewy Bodies (LB), the pathological hallmarks of Parkinson’s Disease. Although LB contain over 70 proteins, the potential for interactions along the aggregation pathway of α-SYN is unknown. Here we propose a map of interactions of 65 proteins against different species of α-SYN. We measured binding to monomeric α-SYN using AlphaScreen, a sensitive nano-bead luminescence assay for detection of protein interactions. To access oligomeric species, we used the pathological mutants of α-SYN (A30P, G51D and A53T) which form oligomers with distinct properties. Finally, we generated amyloid fibrils from recombinant α-SYN. Binding to oligomers and fibrils was measured by two-color coincidence detection (TCCD) on a single molecule spectroscopy setup. Overall, we demonstrate that LB components are recruited to specific steps in the aggregation of α-SYN, uncovering future targets to modulate aggregation in synucleinopathies. To better understand the specific cascade of protein interactions that lead to the pathological aggregation of α-synuclein (wild-type and mutant forms), Leitão et al. present a method to measure interactions of monomeric, oligomeric, and fibrillar forms of α-syn with 65 proteins that were previously shown to be components of Lewy bodies. This approach is useful to understand the sequence of protein-binding events that lead to α-syn aggregation.
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DOI：
10.1073/pnas.1421204112
发表时间：
2015-04-21
影响因子：
11.1
作者：
Chen, Serene W.;Drakulic, Srdja;Cremades, Nunilo
通讯作者：
Cremades, Nunilo
影响因子：
4.8
作者：
Froula, Jessica M.;Castellana-Cruz, Marta;Volpicelli-Daley, Laura A.
通讯作者：
Volpicelli-Daley, Laura A.
鉴定与单体和寡聚 α-突触核蛋白结合的突触体蛋白。
影响因子：
3.7
作者：
Betzer C;Movius AJ;Shi M;Gai WP;Zhang J;Jensen PH
通讯作者：
Jensen PH
DOI：
10.1002/anie.202014898
发表时间：
2021-05-17
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Bhumkar A;Magnan C;Lau D;Jun ESW;Dzamko N;Gambin Y;Sierecki E
通讯作者：
Sierecki E
DOI：
10.1073/pnas.97.2.571
发表时间：
2000-01-18
影响因子：
11.1
作者：
Conway, KA;Lee, SJ;Lansbury, PT
通讯作者：
Lansbury, PT