Amyloid particles facilitate surface-catalyzed cross-seeding by acting as promiscuous nanoparticles
Amyloid particles facilitate surface-catalyzed cross-seeding by acting as promiscuous nanoparticles
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淀粉样蛋白颗粒通过充当混杂的纳米颗粒来促进表面催化的交叉播种
DOI：
10.1101/2020.09.01.278481
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Koloteva-Levine N
中科院分区：
文献类型：
--
作者：
Koloteva-Levine N
淀粉样蛋白种子是纳米大小的蛋白质颗粒，其加速淀粉样蛋白组装以及传播和传递与广泛的蛋白质错误折叠疾病相关的淀粉样蛋白构象。然而，种子淀粉样蛋白的生长，通过模板化的延伸在原纤维末端不能解释整个分子行为的过程中观察到的异源种子的淀粉样蛋白的交叉接种形成。在这里，我们证明了淀粉样蛋白种子可以通过表面催化机制加速淀粉样蛋白的形成，而不传播与种子相关的特定淀粉样蛋白构象。通过对涉及两种非同源和不相关蛋白质（人Aβ42肽和酵母朊病毒形成蛋白Sup35NM）的交叉接种组装反应进行定量表征，证明了这种接种机制。我们的研究结果表明，实验方法来区分播种的模板化延伸从nontemplated淀粉样蛋白播种和合理化的分子机制的交叉播种现象的表现异常的表面活性淀粉样蛋白种子作为纳米粒子。
Amyloid seeds are nanometer-sized protein particles that accelerate amyloid assembly as well as propagate and transmit the amyloid protein conformation associated with a wide range of protein misfolding diseases. However, seeded amyloid growth through templated elongation at fibril ends cannot explain the full range of molecular behaviors observed during cross-seeded formation of amyloid by heterologous seeds. Here, we demonstrate that amyloid seeds can accelerate amyloid formation via a surface catalysis mechanism without propagating the specific amyloid conformation associated with the seeds. This type of seeding mechanism is demonstrated through quantitative characterization of the cross-seeded assembly reactions involving two nonhomologous and unrelated proteins: the human Aβ42 peptide and the yeast prion–forming protein Sup35NM. Our results demonstrate experimental approaches to differentiate seeding by templated elongation from nontemplated amyloid seeding and rationalize the molecular mechanism of the cross-seeding phenomenon as a manifestation of the aberrant surface activities presented by amyloid seeds as nanoparticles.
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影响因子：
3.3
作者：
I. Derkatch;Y. Chernoff;V. Kushnirov;S. Inge-Vechtomov;S. Liebman
通讯作者：
I. Derkatch;Y. Chernoff;V. Kushnirov;S. Inge-Vechtomov;S. Liebman
影响因子：
5.6
作者：
Kumar, Harish;Udgaonkar, Jayant B.
通讯作者：
Udgaonkar, Jayant B.
通过魔法揭示动态朊病毒。
影响因子：
--
作者：
Tuite MF
通讯作者：
Tuite MF
作者回应：淀粉样蛋白聚集体的物理尺寸控制其作为朊病毒颗粒的感染潜力
DOI：
--
发表时间：
2017
期刊：
影响因子：
--
作者：
Ricardo Marchante;David M. Beal;Nadejda Koloteva;T. Purton;M. Tuite;Wei
通讯作者：
Wei
影响因子：
11.4
作者：
Uptain, SM;Sawicki, GJ;Lindquist, S
通讯作者：
Lindquist, S