Mechanistic basis for a molecular triage reaction.
Mechanistic basis for a molecular triage reaction.
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DOI：
10.1126/science.aah6130
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发表时间：
2017-01-20
期刊：
影响因子：
--
通讯作者：
Hegde RS
中科院分区：
文献类型：
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作者：
Shao S;Rodrigo-Brenni MC;Kivlen MH;Hegde RS
新合成的蛋白质在生物合成和降解之间进行分类以维持细胞内稳态，但决策机制尚不清楚。在这里，我们重建的核心反应膜靶向和泛素化的新生尾锚定膜蛋白，以了解它们的命运是如何确定的。中央六组件分流系统分为一个未承诺的客户SGTA复杂，一个自给自足的目标模块，和一个嵌入式，但自给自足的质量控制模块。靶向模块的客户端-SGTA参与诱导快速、私密和承诺的客户端转移到TRC 40以成功生物合成。对泛素化的承诺主要由相对较慢的客户端从SGTA解离和质量控制模块的Bag 6亚基的非私人捕获决定。这提供了一个范例，优先级和时间是如何编码在一个多伴侣分诊系统。
Newly synthesized proteins are triaged between biosynthesis and degradation to maintain cellular homeostasis, but the decision-making mechanisms are unclear. Here, we reconstitute the core reactions for membrane targeting and ubiquitination of nascent tail-anchored membrane proteins to understand how their fate is determined. The central six-component triage system is divided into an uncommitted client-SGTA complex, a self-sufficient targeting module, and an embedded but self-sufficient quality control module. Client-SGTA engagement of the targeting module induces rapid, private, and committed client transfer to TRC40 for successful biosynthesis. Commitment to ubiquitination is dictated primarily by comparatively slower client dissociation from SGTA and non-private capture by the Bag6 subunit of the quality control module. This provides a paradigm for how priority and time are encoded within a multi-chaperone triage system.