转胺酶2对放松的纤维蛋白纤维比拉伸的纤维蛋白纤维具有更高的亲和力
Kateryna Selcuk1, Alexander Leitner2, Lukas Braun1
1Department of Health Sciences and Technology, Institute of Translational Medicine, Laboratory of Applied Mechanobiology, ETH Zurich, Gloriastrasse 37-39 GLC G11, CH-8092 Zurich, Switzerland.
Matrix biology : journal of the International Society for Matrix Biology
|December 22, 2023
概括
转胺酶2 (TG2) 作为纤维菌素 (FN) 纤维的张力传感器,首选与低张力纤维结合. 这种机械调节会影响细胞行为和组织过程.
科学领域:
- 生物化学 生物化学
- 细胞生物学 细胞生物学
- 机械生物学 机械生物学
背景情况:
- 转胺酶2 (TG2) 通过交叉链接稳定细胞外基质 (ECM) 蛋白,并非共性结合纤维素 (FN),这对细胞功能至关重要.
- TG2与纤维状FN,特别是不溶性纤维之间的相互作用尚不清楚.
- 之前的研究集中在可溶或吸附的FN,它们的构造与不溶性FN纤维不同.
研究的目的:
- 为了研究TG2与纤维状纤维素 (FN) 的结合的机械调节.
- 阐明在机械张力下TG2-FN相互作用的分子机制.
- 为了确定TG2和FN之间新的相互作用点.
主要方法:
- 采用了体外FN纤维拉伸试验来研究在不同机械张力下TG2-FN相互作用.
- 采用交联质谱 (XL-MS) 来识别TG2-FN协同场所.
- 集成的XL-MS数据与分子对接,以建模机械调节的结合机制.
主要成果:
- 结合FN的TG2是机械调节的,具有偏好的与低电压FN纤维的同定位.
- 纤维拉伸显著降低了TG2对FN纤维的亲和力.
- 在TG2的C端β桶中确定了一个新的TG2-FN协同位点,与 kanonical凝结合域 (FNI2和FNIII14-15) 外的FN区域相互作用.
- 机械力通过TG2与FN模块FNI7-9.9的相互作用来调节TG2-FN相互作用.
结论:
- TG2 作为 FN 纤维的张力传感器,其结合亲和力由机械力调节.
- 这种机械调节的相互作用机制对理解ECM张力如何影响细胞粘附,迁移和表型具有重要意义.
- 这些发现揭示了ECM动态和细胞矩阵交叉声调的新调节层.
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