Folding path of P5abc RNA involves direct coupling of secondary and tertiary structures.

Folding path of P5abc RNA involves direct coupling of secondary and tertiary structures.
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DOI:
10.1093/nar/gks468
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发表时间:
2012-09
影响因子:
14.9
通讯作者:
Woodson SA
Woodson SA
中科院分区:
生物学2区
文献类型:
--
作者:
Koculi E;Cho SS;Desai R;Thirumalai D;Woodson SA

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二级结构通过三级相互作用的形成而稳定的折叠机制在蛋白质折叠中有很好的记载,但挑战了通常为RNA假设的折叠层次。然而,越来越清楚的是,RNA可以通过类似的机制折叠。P5 abc是嗜热四膜虫I组核酶的一个小的独立折叠三级结构域,已知通过涉及螺旋P5 c的二级结构重排折叠。然而,这种重排的程度和触发它的折叠的精确阶段是未知的。我们使用实验和模拟表明,P5 c螺旋开关的天然二级结构后期的折叠途径,并直接耦合到形成的三级相互作用中的A-丰富的凸起。P5 c突变表明,在P5 c的开关是不是速率决定,并建议在P5 c的非天然的相互作用,帮助折叠,而不是阻碍it. Our研究表明,尽管在蛋白质和RNA的构建模块的显着差异,可能有共同的方式,他们自组装。
Folding mechanisms in which secondary structures are stabilized through the formation of tertiary interactions are well documented in protein folding but challenge the folding hierarchy normally assumed for RNA. However, it is increasingly clear that RNA could fold by a similar mechanism. P5abc, a small independently folding tertiary domain of the Tetrahymena thermophila group I ribozyme, is known to fold by a secondary structure rearrangement involving helix P5c. However, the extent of this rearrangement and the precise stage of folding that triggers it are unknown. We use experiments and simulations to show that the P5c helix switches to the native secondary structure late in the folding pathway and is directly coupled to the formation of tertiary interactions in the A-rich bulge. P5c mutations show that the switch in P5c is not rate-determining and suggest that non-native interactions in P5c aid folding rather than impede it. Our study illustrates that despite significant differences in the building blocks of proteins and RNA, there may be common ways in which they self-assemble.
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