腺三聚酸和三聚酸的非特异性结合调节了lyszyme的相位行为
Matja Zalar1, Jordan Bye1, Robin Curtis1
1Manchester Institute of Biotechnology, Department of Chemical Engineering, Faculty of Science and Engineering, The University of Manchester, 131 Princess Street, ManchesterM1 7DN, U.K.
Journal of the American Chemical Society
|January 6, 2023
概括
氨酸三聚酸 (ATP) 不特定地与酶等蛋白质结合,影响蛋白质的溶解性和聚合. 这种相互作用主要通过聚酸盐组对蛋白质结晶和细胞过程产生影响.
科学领域:
- 生物化学
- 结构生物学
- 生物物理
背景情况:
- 已知腺三聚酸盐 (ATP) 与蛋白质相互作用,影响生物分子凝聚物形成和蛋白质聚合.
- 非特异性蛋白与ATP相互作用的确切性质及其对蛋白质溶解性的影响在很大程度上仍未得到描述.
研究的目的:
- 阐明ATP与模型蛋白质lyszyme的详细结合特性.
- 研究ATP结合对蛋白质可溶性,聚合和结晶的影响.
主要方法:
- 使用X射线结晶学来确定ATP结合的结构基础.
- 用核磁共振 (NMR) 光谱识别ATP结合点并描述结合亲缘关系.
- 溶液阶段的蛋白质与蛋白质相互作用研究在不同的盐度和的存在下进行.
主要成果:
- 在溶酶上发现了6个ATP结合位点:一个已知的高亲和位点和5个具有毫米亲和度的新型非特异位点,它们也结合三聚酸盐 (TPP).
- 主要通过其多酸盐部分,ATP结合主要发生在非特定位点的氨酸残留物上.
- ATP和TPP对蛋白质与蛋白质的相互作用具有相似的影响,在低度下诱导沉,在更高度下重新溶解.
- 添加到ATP并没有影响结合亲和力,但阻止了酶沉.
结论:
- 在生理条件下,ATP主要通过其多酸盐组与折叠的蛋白质结合.
- 结合ATP会影响蛋白质的溶解性,并可以防止蛋白质的聚合,并确定了潜在的机制.
- 这些发现为蛋白质结晶策略和ATP在细胞蛋白质平衡中的作用提供了洞察力.
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