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水在野生类型和突变型トランスチレチン复合物的稳定性中起着关键作用

Carter Lantz¹, Robert L Rider¹, Sangho D Yun¹

¹Department of Chemistry, Texas A&M University, College Station, Texas 77843, United States.

Journal of the American Society for Mass Spectrometry

|July 26, 2024

概括

晶氨酸 (TTR) 四聚合物稳定性和氨基粉症风险受到亚单元交换的影响,尤其是在较低的温度下. 混合型TTR四基体自发形成,影响疾病的进展.

科学领域:

生物化学生物化学
结构生物学结构生物学
生物物理学的生物物理.

背景情况:

晶氨酸 (TTR) 四基对甲状腺素和视网醇的运输至关重要.
在氨基粉症中,TTR四聚合物分离成单聚合物,二聚合物和三聚合物有关.
在异卵性个体中,混合TTR (hTTR) 四分体显示粉样性粉症的比率增加.

研究的目的:

为了研究跨氨酸亚单位交换 (SUE) 反应.
分析初级结构和温度对TTR四聚体稳定性和hTTR形成的影响.
探索水网络在TTR四相稳定中的作用.

主要方法:

使用高分辨率原生质谱 (nMS) 来监测SUE反应.
在不同温度条件下对同质和混合TTR四度体的分析.
对不同TTR突变 (L55P,V30M,F87A,T119M) 的SUE行为进行比较.

主要成果:

在TTR初级结构的差异影响四聚体稳定性.
通过SUE反应观察到hTTR产物的自发形成.
较低的温度显著促进了具有L55P和V30M突变的hTTR形成.
温度对具有F87A和T119M突变的HTTR形成的影响较小.

结论:

TTR四聚合物稳定性和SUE动态受主要结构和温度的影响.
观察到的取决于温度的稳定性可能与补水网络有关.
高分辨率的nMS是一种有价值的工具,用于研究蛋白质复合体的动态和稳定性相关的粉样化症.

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