Growth factor receptor-bound 2 (Grb2) is an important link in the receptor tyrosine kinase signaling cascades. It is involved in crucial processes, both physiological (mainly embryogenesis) and pathological (different types of cancer). Several binding partners of all three domains (SH3–SH2–SH3) of this adaptor protein are well described, such as ErbB family members for the SH2 domain and Sos for the SH3 domains. How the different domains interact with each other, both structurally and functionally, is still unclear. These interactions could be essential for regulation processes, and therefore are of great interest. Although a lot of structural data on Grb2 exist, they describe either individual domains, ligand-bound conformations, or frozen pictures of the protein captured by crystallography. Here we report the assignment of backbone and of \(^{13}\hbox {C}_\beta\) chemical shifts of full-length, apo-Grb2 in solution. In addition to the assigned conformation corresponding to three well-folded domains, a set of peaks compatible with the presence of an unfolded conformation of the N-terminal SH3 domain is observed. This assignment paves the way for future studies of inter-domain interactions and dynamics that have to be taken into account when studying the regulation of Grb2 interactions and signaling pathways.

中文翻译：

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[公式：见正文]H、[公式：见正文]C和[公式：见正文]N个不含配体的人Grb2的分配。

生长因子受体结合 2 (Grb2) 是受体酪氨酸激酶信号级联反应中的重要环节。它参与生理（主要是胚胎发生）和病理（不同类型的癌症）的关键过程。该衔接蛋白的所有三个域 (SH3–SH2–SH3) 的几个结合配偶体都有很好的描述，例如 SH2 域的 ErbB 家族成员和 SH3 域的 Sos。不同的域如何在结构和功能上相互作用，目前还不清楚。这些相互作用对于监管过程可能是必不可少的，因此引起了极大的兴趣。尽管存在大量关于 Grb2 的结构数据，但它们描述了单个域、配体结合构象或晶体学捕获的蛋白质的冷冻图片。在这里，我们报告了骨干和\(^{13}\hbox {C}_\beta\)溶液中全长 apo-Grb2 的化学位移。除了对应于三个折叠良好的结构域的指定构象外，还观察到一组与 N 端 SH3 结构域未折叠构象的存在兼容的峰。这项任务为未来研究 Grb2 相互作用和信号通路的调节时必须考虑的域间相互作用和动力学铺平了道路。