BACKGROUND Sorcin is a calcium sensor that exerts many calcium-related functions in the cells, e.g. it regulates calcium concentration in the cytoplasm, endoplasmic reticulum (ER) and mitochondria, by interacting with calcium pumps, exchangers and channels. Albeit Sorcin is an interesting potential cancer target, little is known about its interactors upon calcium-mediated activation. Our previous study suggested that Sorcin may recognize short linear binding motifs as the crystal structure revealed a self-interaction with a GYYPGG stretch in its N-terminus, and combinatorial peptide-phage display provided support for peptide-mediated interactions. METHODS In this study we screened for motif-based interactions between Sorcin and intrinsically disordered regions of the human proteome using proteomic peptide phage display (ProP-PD). We identified a peptide belonging to protein phosphatase 1 regulatory subunit 3G (PPP1R3G) as a potential novel interactor and confirm the interaction through biophysical and cell-based approaches, and provide structural information through molecular dynamics simulations. RESULTS Altogether, we identify a preferred motif in the enriched pool of binders and a peptide belonging to protein phosphatase 1 regulatory subunit 3G (PPP1R3G) as a preferred ligand. CONCLUSION Through this study we gain information on a new Sorcin binding partner and profile Sorcin's motif-based interaction. GENERAL SIGNIFICANCE The interaction between Sorcin and PPP1R3G may suggest a close dependence between glucose homeostasis and calcium concentration in the different cell compartments, opening a completely new and interesting scenery yet to be fully disclosed.

中文翻译：

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Sorcin与人类蛋白质组的内在无序区域之间的钙依赖性相互作用的分析。

背景技术Sorcin是一种钙传感器，其在细胞中发挥许多与钙有关的功能，例如，它通过与钙泵，交换子和通道​​相互作用来调节细胞质，内质网（ER）和线粒体中的钙浓度。尽管索辛是一个有趣的潜在癌症靶标，但对于其在钙介导的活化作用下的相互作用者知之甚少。我们以前的研究表明Sorcin可能识别短的线性结合基序，因为其晶体结构揭示了在其N末端与GYYPGG延伸区发生自我相互作用，并且组合肽噬菌体展示为肽介导的相互作用提供了支持。方法在这项研究中，我们使用蛋白质组肽噬菌体展示（ProP-PD）筛选了Sorcin与人类蛋白质组的内在无序区域之间基于基序的相互作用。我们确定了属于蛋白质磷酸酶1调节亚基3G（PPP1R3G）的肽作为潜在的新型相互作用子，并通过生物物理和基于细胞的方法确认了相互作用，并通过分子动力学模拟提供了结构信息。结果总的来说，我们在富集的结合剂和属于蛋白质磷酸酶1调节亚基3G（PPP1R3G）的肽中鉴定了优选的基序作为优选的配体。结论通过这项研究，我们获得了有关新的Sorcin结合伴侣的信息，并介绍了Sorcin基于基序的相互作用。一般意义Sorcin和PPP1R3G之间的相互作用可能表明葡萄糖稳态与不同细胞室中钙浓度之间存在密切相关性，从而开辟了一个崭新而有趣的风景，有待充分揭示。