A model for gain of function in superoxide dismutase
A model for gain of function in superoxide dismutase
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DOI：
10.1016/j.bbrep.2020.100728
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发表时间：
2020-03-01
影响因子：
2.7
通讯作者：
Toledo, Santiago
中科院分区：
文献类型：
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作者：
Healy, Eamonn F.;Roth-Rodriguez, Analise;Toledo, Santiago
研究发现，突变的、错误折叠的超氧化物歧化酶[Cu-Zn]（SOD 1）可以以朊病毒样方式转化野生型SOD 1（wtSOD 1），并且错误折叠的wtSOD 1可以通过释放和摄取蛋白质聚集体来繁殖。在开发一种类似朊病毒的机制，这种传播的SOD 1错误折叠，我们以前已经表明如何enervation的SOD 1静电环（ESL），造成的短暂的非专性的SOD 1寡聚体的形成，可以导致实验观察到的增益的相互作用（GOI），结果在形成的SOD 1淀粉样蛋白样丝。它也已被证明，ESL运动的自由是必不可少的催化功能。这项工作调查的可能性，限制ESL的流动性可能不仅损害超氧化物催化活性，但也有助于促进过氧化物酶活性的SOD 1，从而暗示形成的SOD 1寡聚体的蛋白质错误折叠和蛋白质氧化。
Studies have found that mutant, misfolded superoxide dismutase [Cu-Zn] (SOD1) can convert wild type SOD1 (wtSOD1) in a prion-like fashion, and that misfolded wtSOD1 can be propagated by release and uptake of protein aggregates. In developing a prion-like mechanism for this propagation of SOD1 misfolding we have previously shown how enervation of the SOD1 electrostatic loop (ESL), caused by the formation of transient non-obligate SOD1 oligomers, can lead to an experimentally observed gain of interaction (GOI) that results in the formation of SOD1 amyloid-like filaments. It has also been shown that freedom of ESL motion is essential to catalytic function. This work investigates the possibility that restricting ESL mobility might not only compromise superoxide catalytic activity but also serve to promote the peroxidase activity of SOD1, thus implicating the formation of SOD1 oligomers in both protein misfolding and in protein oxidation.