Stability of 20S Proteasome Configurations: Preopening the Axial Gate.
Stability of 20S Proteasome Configurations: Preopening the Axial Gate.
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20S 蛋白酶体配置的稳定性：预打开轴门。
DOI：
10.1021/acs.jpclett.3c01040
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Clemmer,DavidE
中科院分区：
文献类型：
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作者：
Henderson,LucasW;Sharon,EdieM;Gautam,AmitKS;Anthony,AdamJ;Jarrold,MartinF;Russell,DavidH;Matouschek,Andreas;Clemmer,DavidE
本品稳定性的质谱分析。从11℃到55℃，cerevisiae20S蛋白酶体揭示了一系列相关的构型和偶联转变，这些结构和偶联转变似乎与蛋白水解核心的打开有关。我们没有发现离解的证据，所有的转变都是可逆的。热力学分析表明，构型可分为三种一般类型的结构：热稳定，紧闭（观察到+54到+58电荷态）构型；高熵（+60 ~ +66）状态被认为是孔隙打开的前兆；较大的（+70 ~ +79）部分和完全开放的孔隙结构。在缺乏19S调控单元的情况下，打开20S孔的机制似乎涉及一个电荷引发过程，使封闭孔结构松动。这些20S前驱体构型中只有一小部分（≤2%）出现打开，从而暴露出催化腔。
Mass spectrometry studies of the stability of theS. cerevisiae20S proteasome from 11 to 55 °C reveal a series of related configurations and coupled transitions that appear to be associated with opening of the proteolytic core. We find no evidence for dissociation, and all transitions are reversible. A thermodynamic analysis indicates that configurations fall into three general types of structures: enthalpically stabilized, tightly closed (observed as the +54 to +58 charge states) configurations; high-entropy (+60 to +66) states that are proposed as precursors to pore opening; and larger (+70 to +79) partially and fully open pore structures. In the absence of the 19S regulatory unit, the mechanism for opening the 20S pore appears to involve a charge-priming process that loosens the closed-pore configuration. Only a small fraction (≤2%) of these 20S precursor configurations appear to open and thus expose the catalytic cavity.