Mechanism of prion propagation: amyloid growth occurs by monomer addition.
Mechanism of prion propagation: amyloid growth occurs by monomer addition.
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DOI：
10.1371/journal.pbio.0020321
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发表时间：
2004-10
期刊：
影响因子：
9.8
通讯作者：
Weissman JS
中科院分区：
文献类型：
--
作者：
Collins SR;Douglass A;Vale RD;Weissman JS
大量的非纤维状低聚物中间体是淀粉样蛋白形成的共同特征，并且这些低聚物，而不是最终的纤维，已被认为是某些淀粉样蛋白疾病中的毒性物质。然而，这种低聚物是否是纤维组装的关键中间体或形成替代的、潜在的可分离途径仍不清楚。在这里，我们研究淀粉样蛋白酵母朊蛋白Sup35的聚合。快速聚合在没有可观察到的中间体的情况下发生，并且有针对性的动力学和直接的单分子荧光测量都表明纤维通过单体加成而生长。一个三步模型（成核，单体加成和纤维断裂）准确地占淀粉样蛋白形成的独特的动力学特征，包括弱浓度依赖性，搅拌加速，和S形的聚合时间过程。因此，淀粉样蛋白生长可以通过在与潜在毒性低聚中间体形成不同且竞争的反应中加入单体而发生。淀粉样蛋白酵母朊病毒蛋白Sup35的聚合通过在与潜在毒性低聚中间体形成不同的反应中单体加成而发生
Abundant nonfibrillar oligomeric intermediates are a common feature of amyloid formation, and these oligomers, rather than the final fibers, have been suggested to be the toxic species in some amyloid diseases. Whether such oligomers are critical intermediates for fiber assembly or form in an alternate, potentially separable pathway, however, remains unclear. Here we study the polymerization of the amyloidogenic yeast prion protein Sup35. Rapid polymerization occurs in the absence of observable intermediates, and both targeted kinetic and direct single-molecule fluorescence measurements indicate that fibers grow by monomer addition. A three-step model (nucleation, monomer addition, and fiber fragmentation) accurately accounts for the distinctive kinetic features of amyloid formation, including weak concentration dependence, acceleration by agitation, and sigmoidal shape of the polymerization time course. Thus, amyloid growth can occur by monomer addition in a reaction distinct from and competitive with formation of potentially toxic oligomeric intermediates. Polymerization of the amyloidogenic yeast prion protein Sup35 occurs by monomer addition in a reaction distinct from formation of potentially toxic oligomeric intermediates
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DOI：
10.1038/nsb786
发表时间：
2002-05-01
期刊：
NATURE STRUCTURAL BIOLOGY
影响因子：
--
作者：
DePace, AH;Weissman, JS
通讯作者：
Weissman, JS
影响因子：
2.9
作者：
Esler, WP;Stimson, ER;Maggio, JE
通讯作者：
Maggio, JE
影响因子：
5.3
作者：
Ness, F;Ferreira, P;Tuite, MF
通讯作者：
Tuite, MF
DOI：
10.1073/pnas.0308754101
发表时间：
2004-02-24
影响因子：
11.1
作者：
Scheibel, T;Bloom, J;Lindquist, SL
通讯作者：
Lindquist, SL
DOI：
10.1016/j.bbrc.2004.01.117
发表时间：
2004-03-12
影响因子：
3.1
作者：
Kishimoto, A;Hasegawa, K;Yoshida, M
通讯作者：
Yoshida, M