Destabilizing mutations promote membrane protein misfolding
Destabilizing mutations promote membrane protein misfolding
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DOI：
10.1021/bi035918s
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发表时间：
2004-01-13
期刊：
影响因子：
2.9
通讯作者：
Sanders, CR
中科院分区：
文献类型：
--
作者：
Nagy, JK;Sanders, CR
在这项工作中，稳定性和错误折叠的倾向之间的关系进行了探讨的一系列纯化的多位整合膜蛋白二酰甘油激酶的变体。观察到稳定性和折叠效率之间存在强相关性。促进错误折叠的最常见突变也是那些使蛋白质不稳定的突变。这些结果意味着通过靶向不稳定的膜蛋白进行降解，细胞蛋白质折叠质量控制可以消除具有高内在倾向错误折叠成异常结构的蛋白质。此外，促进错误折叠而不干扰稳定性的更罕见的氨基酸突变类型可能特别危险，因为突变蛋白质可能逃避细胞质量控制系统的监督。
In this work, the relationship between stability and propensity to misfold was probed for a series of purified variants of the polytopic integral membrane protein diacylglycerol kinase. It was observed that there was a strong correlation between stability and folding efficiency. The most common mutations that promoted misfolding were those which also destabilized the protein. These results imply that by targeting unstable membrane proteins for degradation, cellular protein folding quality control can eliminate proteins that have a high intrinsic propensity to misfold into aberrant structures. Moreover, the more rare class of amino acid mutations that promote misfolding without perturbing stability may be particularly dangerous because the mutant proteins may evade the surveillance of cellular quality control systems.