Healy Eamonn F, Roth-Rodriguez Analise, Toledo Santiago
Department of Chemistry, St. Edward's University, Austin, TX, 78704, USA.
Biochem Biophys Rep. 2020 Jan 14;21:100728. doi: 10.1016/j.bbrep.2020.100728. eCollection 2020 Mar.
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.
研究发现，突变的、错误折叠的超氧化物歧化酶[铜锌]（SOD1）能够以朊病毒样方式转化野生型SOD1（wtSOD1），并且错误折叠的wtSOD1能够通过蛋白质聚集体的释放和摄取进行传播。在为SOD1错误折叠的这种传播建立一种朊病毒样机制的过程中，我们之前已经表明，由短暂的非 obligate SOD1寡聚体形成所导致的SOD1静电环（ESL）的去神经支配，如何能够导致实验观察到的相互作用增强（GOI），从而导致SOD1淀粉样细丝的形成。还表明ESL运动的自由度对于催化功能至关重要。这项工作研究了限制ESL流动性不仅可能损害超氧化物催化活性，而且还可能促进SOD1的过氧化物酶活性的可能性，从而表明SOD1寡聚体的形成在蛋白质错误折叠和蛋白质氧化中都起作用。
