Bag6 complex contains a minimal tail-anchor-targeting module and a mock BAG domain
Bag6 complex contains a minimal tail-anchor-targeting module and a mock BAG domain
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DOI：
10.1073/pnas.1402745112
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发表时间：
2015-01-06
影响因子：
11.1
通讯作者：
Clemons, William Melvon, Jr.
中科院分区：
文献类型：
--
作者：
Mock, Jee-Young;Chartron, Justin William;Clemons, William Melvon, Jr.
BCL2 相关的 athanogene cochaperone 6 (Bag6) 在多种过程中的细胞稳态中发挥着核心作用，并且是异源三聚体 Bag6 复合物的一部分，该复合物还包括泛素样 4A (Ubl4A) 和跨膜结构域识别复合物 35 (TRC35)。该复合物最近已被证明在 TRC 途径、错误定位的蛋白质降解途径和内质网相关降解途径中很重要。在这里，我们定义了 Bag6 复合体的架构，证明 TRC35 和 Ubl4A 在 Bag6 上具有不同的 C 端结合位点，定义了最小的 Bag6 复合体。 Bag6-Ubl4A 二聚体的晶体结构表明 Bag6-BAG 不是典型的 BAG 结构域，并且这一发现得到了生物化学的证实。值得注意的是，此处定义的最小 Bag6 复合物促进尾部锚定底物从富含谷氨酰胺的小四三肽重复序列蛋白 a 转移到 TRC40。这些发现提供了对 Bag6 协调的复杂蛋白质网络的结构见解。
BCL2-associated athanogene cochaperone 6 (Bag6) plays a central role in cellular homeostasis in a diverse array of processes and is part of the heterotrimeric Bag6 complex, which also includes ubiquitin-like 4A (Ubl4A) and transmembrane domain recognition complex 35 (TRC35). This complex recently has been shown to be important in the TRC pathway, the mislocalized protein degradation pathway, and the endoplasmic reticulum-associated degradation pathway. Here we define the architecture of the Bag6 complex, demonstrating that both TRC35 and Ubl4A have distinct C-terminal binding sites on Bag6 defining a minimal Bag6 complex. A crystal structure of the Bag6-Ubl4A dimer demonstrates that Bag6-BAG is not a canonical BAG domain, and this finding is substantiated biochemically. Remarkably, the minimal Bag6 complex defined here facilitates tail-anchored substrate transfer from small glutamine-rich tetratricopeptide repeat-containing protein a to TRC40. These findings provide structural insight into the complex network of proteins coordinated by Bag6.