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首页> 外文期刊>Journal of Molecular Biology >The metavinculin tail domain directs constitutive interactions with raver1 and vinculin RNA
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The metavinculin tail domain directs constitutive interactions with raver1 and vinculin RNA

机译：metavinculin尾结构域指导与raver1和长春花蛋白RNA的组成性相互作用

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摘要

Vinculin is a key regulator of the actin cytoskeleton attachment to the cell membrane at cellular adhesion sites, which is crucial for processes such as cell motility and migration, development, survival, and wound healing. Vinculin loss results in embryonic lethality, cardiovascular diseases, and cancer. Its tail domain, Vt, is crucial for vinculin activation and focal adhesion turnover and binds to the actin cytoskeleton and acidic phospholipids upon which it unfurls. The RNA binding protein raver1 regulates the assembly of focal adhesions transcriptionally by binding to vinculin. The muscle-specific splice form, metavinculin, is characterized by a 68-residue insert in the tail domain (MVt) and correlates with hereditary idiopathic dilated cardiomyopathy. Here, we report that metavinculin can bind to raver1 in its inactive state. Our crystal structure explains this permissivity, where an extended coil unique to MVt is unfurled in the MVtΔ954:raver1 complex structure. Our binding assays show that raver1 forms a ternary complex with MVt and vinculin mRNA. These findings suggest that the metavinculin:raver1:RNA complex is constitutively recruited to adhesion complexes.
机译：Vinculin是肌动蛋白细胞骨架在细胞粘附位点附着在细胞膜上的关键调节剂，这对于诸如细胞运动和迁移，发育，存活和伤口愈合等过程至关重要。长春花蛋白的损失会导致胚胎致死率，心血管疾病和癌症。它的尾部结构域Vt对纽蛋白活化和粘着斑转换至关重要，并与肌动蛋白的细胞骨架和酸性磷脂结合，从而解开。 RNA结合蛋白raver1通过结合纽扣蛋白在转录上调节粘着斑的组装。肌肉特异性剪接形式metavinculin的特征是在尾部区域（MVt）中有68个残基，并且与遗传性特发性扩张型心肌病相关。在这里，我们报道了metavinculin可以以非活性状态与raver1结合。我们的晶体结构解释了这种介电常数，其中MVt特有的扩展线圈在MVtΔ954：raver1复杂结构中展开。我们的结合试验表明，raver1与MVt和纽扣蛋白mRNA形成三元复合物。这些发现表明，metavinculin：raver1：RNA复合物是组成型募集的粘附复合物。

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