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首页> 外文期刊>Biophysical Chemistry: An International Journal Devoted to the Physical Chemistry of Biological Phenomena >Interaction of ERp57 with calreticulin: Analysis of complex formation and effects of vancomycin
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Interaction of ERp57 with calreticulin: Analysis of complex formation and effects of vancomycin

机译:ERp57与钙网蛋白的相互作用:万古霉素的复合物形成和作用分析

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摘要

The protein ERp57 (also known as PDIA3) is a widely distributed protein, mainly localized in the endoplasmic reticulum, where it acts as disulfide isomerase, oxidoreductase and chaperone, in concert with the lectins calreticulin (CRT) and calnexin. The ERp57/CRT complex has been detected on the cell surface and previous studies have suggested its involvement in programmed cell death. Although the ERp57-CRT complex has been characterized, little is known about its role in different cellular compartments as well as inhibitors of this interaction. We focused on the kinetic, extent and stability of the ERp57-CRT complex, using the surface plasmon resonance spectroscopy, investigating the possible role as inhibitor of the antibiotic vancomycin. Equilibrium thermodynamic data suggested that vancomycin may hinder the interaction between the two proteins and could interfere with the ERp57 conformational changes that stabilize the complex. Furthermore, by means of confocal microscopy, we evaluated the effect of the in vivo administration of vancomycin on the ERp57/CRT complex on the surface of HeLa cells. The model presented here could be used for the search of other specific inhibitors/interactors of ERp57, which can be extremely helpful to understand the biological pathways where the protein is involved and to modulate its activity.
机译:ERp57蛋白(也称为PDIA3)是一种分布广泛的蛋白,主要位于内质网中,与凝集素钙网蛋白(CRT)和钙粘蛋白协同作用,充当二硫键异构酶,氧化还原酶和伴侣蛋白。 ERp57 / CRT复合物已在细胞表面被检测到,以前的研究表明它参与了程序性细胞死亡。尽管已鉴定出ERp57-CRT复合物,但对其在不同细胞区室中的作用以及这种相互作用的抑制剂知之甚少。我们利用表面等离子体共振光谱研究了ERp57-CRT复合物的动力学,范围和稳定性,研究了其作为抗生素万古霉素抑制剂的可能作用。平衡热力学数据表明,万古霉素可能会阻碍这两种蛋白质之间的相互作用,并可能干扰稳定该复合物的ERp57构象变化。此外,借助共聚焦显微镜,我们评估了体内万古霉素对HeLa细胞表面ERp57 / CRT复合物的作用。此处介绍的模型可用于搜索ERp57的其他特异性抑制剂/相互作用物,这对于了解蛋白质所涉及的生物学途径并调节其活性可能非常有帮助。

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