Molecular Architecture and Function of the SEA Complex, a Modulator of the TORC1 Pathway
Molecular Architecture and Function of the SEA Complex, a Modulator of the TORC1 Pathway
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DOI：
10.1074/mcp.m114.039388
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发表时间：
2014-11-01
影响因子：
7
通讯作者：
Dokudovskaya, Svetlana
中科院分区：
文献类型：
--
作者：
Algret, Romain;Fernandez-Martinez, Javier;Dokudovskaya, Svetlana
TORC1信号通路在控制细胞生长和应激反应中起重要作用。在这里，我们证明SEA复合体与TORC1物理相互作用，并且是其活性的重要调节因子。在氮饥饿期间，SEA复合物组分的缺失导致Tor1激酶脱位，自噬缺陷和液泡断裂。TORC1失活，通过氮剥夺或雷帕霉素治疗，改变SEA复合体成员的细胞水平。我们使用亲和纯化和化学交联来生成用于综合结构建模方法的数据，该方法产生了SEA复合体的明确的分子结构，并表明SEA复合体包括结构和功能不同的两个区域。SEA复合体作为一个平台出现，可以协调TORC1途径有效运作所必需的结构和酶活性。
The TORC1 signaling pathway plays a major role in the control of cell growth and response to stress. Here we demonstrate that the SEA complex physically interacts with TORC1 and is an important regulator of its activity. During nitrogen starvation, deletions of SEA complex components lead to Tor1 kinase delocalization, defects in autophagy, and vacuolar fragmentation. TORC1 inactivation, via nitrogen deprivation or rapamycin treatment, changes cellular levels of SEA complex members. We used affinity purification and chemical cross-linking to generate the data for an integrative structure modeling approach, which produced a well-defined molecular architecture of the SEA complex and showed that the SEA complex comprises two regions that are structurally and functionally distinct. The SEA complex emerges as a platform that can coordinate both structural and enzymatic activities necessary for the effective functioning of the TORC1 pathway.