阿尔法-酸蛋白酶的未折叠构造比其原始状态更稳定
J L Sohl1, S S Jaswal, D A Agard
1Graduate Group in Biophysics, Howard Hughes Medical Institute, University of California at San Francisco, 94143-0448, USA.
Nature
|October 31, 1998
概括
阿尔法-酸蛋白酶 (alphaLP) 的亲区域对其折叠至关重要. 在阿尔法LPLP.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 蛋白质折叠 蛋白质的折叠
背景情况:
- 细胞外细菌蛋白质酶,如α-Lytic蛋白质酶 (alphaLP),与必要的亲区域进行合成.
- 亲区域促进了体内和体外适当的蛋白质折叠.
研究的目的:
- 调查亲区域在alphaLP折叠和稳定性中的作用.
- 为了确定alphaLP折叠和展开的自由能量景观.
主要方法:
- 蛋白质工程来消除亲区域.
- 循环二重化谱法用于评估蛋白质折叠.
- 差分扫描热量计用于测量热稳定性.
- 免费能量计算以建模折叠路径.
主要成果:
- 阿尔法LP的亲区域对于实现本地,活跃状态至关重要.
- 在缺少亲区域的情况下,alphaLP折叠成一个不活跃的,部分折叠的状态 (I).
- 亲区域稳定了折叠过渡状态,降低了折叠的激活能量.
- 无论是alphaLP的非活性状态 (I) 还是未折叠状态,都在热力学上比原始状态更稳定.
- 原生alphaLP是转移稳定的,稳定性取决于高动力障碍的展开,而不是有利的自由能量差异.
结论:
- 阿尔法LP的原始状态是动力产物,而不是热力学产物.
- 对alphaLP的蛋白质进化优先考虑一个大型展开的障碍,而不是最小化自由能量.
- 亲区域为alphaLP起到关键的折叠催化剂和动力稳定剂的作用.
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