Structure of human mTORC1 components The mTORC1 (mechanistic target of rapamycin complex 1) complex garners much attention as a signaling hub that coordinates input from growth-factor receptors and nutrient availability with metabolism and cell growth and proliferation. de Araujo et al. report the crystal structure of the LAMTOR (or “Ragulator”) complex that helps assemble mTORC1 at the lysosomal membrane for activation. The structure and functional studies reveal how LAMTOR1 wraps around the other subunits to hold them in place and interacts with the Rag guanosine triphosphatases in the complex. Science, this issue p. 377 Structural insights into nutrient and growth factor signaling at the lysosome. The LAMTOR [late endosomal and lysosomal adaptor and MAPK (mitogen-activated protein kinase) and mTOR (mechanistic target of rapamycin) activator] complex, also known as “Ragulator,” controls the activity of mTOR complex 1 (mTORC1) on the lysosome. The crystal structure of LAMTOR consists of two roadblock/LC7 domain–folded heterodimers wrapped and apparently held together by LAMTOR1, which assembles the complex on lysosomes. In addition, the Rag guanosine triphosphatases (GTPases) associated with the pentamer through their carboxyl-terminal domains, predefining the orientation for interaction with mTORC1. In vitro reconstitution and experiments with site-directed mutagenesis defined the physiological importance of LAMTOR1 in assembling the remaining components to ensure fidelity of mTORC1 signaling. Functional data validated the effect of two short LAMTOR1 amino acid regions in recruitment and stabilization of the Rag GTPases.

中文翻译：

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人溶酶体 mTORC1 支架复合物的晶体结构及其对信号传导的影响

人类 mTORC1 组分的结构 mTORC1（雷帕霉素复合物 1 的机械靶标）复合物作为信号中枢而备受关注，该中枢可协调来自生长因子受体的输入和营养可用性与代谢和细胞生长和增殖。德阿劳霍等人。报告了 LAMTOR（或“Ragulator”）复合物的晶体结构，该复合物有助于在溶酶体膜上组装 mTORC1 以进行激活。结构和功能研究揭示了 LAMTOR1 如何包裹其他亚基以将它们固定到位并与复合物中的 Rag 鸟苷三磷酸酶相互作用。科学，这个问题 p。377 对溶酶体营养和生长因子信号的结构洞察。LAMTOR [晚期内体和溶酶体接头和 MAPK（丝裂原活化蛋白激酶）和 mTOR（雷帕霉素的机械靶标）激活剂] 复合物，也称为“调节剂”，控制着 mTOR 复合物 1 (mTORC1) 在溶酶体上的活性。LAMTOR 的晶体结构由两个路障/LC7 结构域折叠的异二聚体组成，它们被 LAMTOR1 包裹并显然保持在一起，LAMTOR1 将复合物组装在溶酶体上。此外，Rag 鸟苷三磷酸酶 (GTPase) 通过其羧基末端结构域与五聚体相关联，预先定义了与 mTORC1 相互作用的方向。体外重组和定点诱变实验确定了 LAMTOR1 在组装其余成分以确保 mTORC1 信号保真度方面的生理重要性。