A mechanism for propagated SOD1 misfolding from frustration analysis of a G85R mutant protein assembly.

A mechanism for propagated SOD1 misfolding from frustration analysis of a G85R mutant protein assembly.
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DOI:
10.1016/j.bbrc.2016.08.172
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发表时间:
2016-09-30
影响因子:
3.1
通讯作者:
Healy EF
Healy EF
中科院分区:
生物学4区
文献类型:
--
作者:
Healy EF

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应用景观理论和Glenon假说的晶体结构的G85R突变超氧化物歧化酶(SOD 1)四聚体复合物允许描述朊病毒样假说,用于解释传播SOD 1错误折叠。我们已经开发了两个构象变化的情况下,一个本地的ESL在复杂的接口,和第二个位移在ESL的另一个二聚体亚基。当将这些结合在一起时,提供了朊病毒样机制,其可以用于解释观察到的由G85R突变体将wtSOD 1转化为错误折叠形式。
Application of landscape theory and the dehydron hypothesis to a crystal structure of a G85R mutant superoxide dismutase (SOD1) tetrameric complex allows for the description of a prion-like hypothesis that serves to explain propagated SOD1 misfolding. We have developed two conformational-change scenarios, one local to the ESL at the complex interface, and a second displacement at the ESL of the another dimeric subunit. When taken together these provide for a prion-like mechanism that can serve to explain the observed conversion of wtSOD1 to a misfolded form by the G85R mutant.
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