Structural basis for dimerization quality control.

Structural basis for dimerization quality control.
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DOI:
10.1038/s41586-020-2636-7
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发表时间:
2020-10
期刊:
影响因子:
64.8
通讯作者:
Rape M
Rape M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Mena EL;Jevtić P;Greber BJ;Gee CL;Lew BG;Akopian D;Nogales E;Kuriyan J;Rape M

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大多数质量控制途径靶向错误折叠的蛋白质,以防止毒性聚集和神经变性。二聚化质量控制(DQC)通过消除异常组成的复合物进一步改善蛋白质稳定,但它如何检测不正确的亚基仍然是未知的。在这里,我们通过SCFFBXL17提供了对靶选择的结构洞察,SCFFBXL17是一种DQC E3连接酶,其泛素化并帮助降解BTB蛋白的非活性异源二聚体,同时保留功能性同源二聚体。我们发现SCFFBXL17破坏了异常的BTB二聚体,这些二聚体不能稳定BTB结构域的高度发散的β链周围的分子间β折叠。复杂的解离允许SCFFBXL17包裹在单个BTB结构域周围,以实现稳健的泛素化。因此,SCFFBXL17探测BTB结构域的形状和互补性,这是一种非常适合于建立经常性相互作用模块的复合物组成的质量控制的机制。
Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration . Dimerization quality control (DQC) further improves proteostasis by eliminating complexes of aberrant composition , yet how it detects incorrect subunits is still unknown. Here, we provide structural insight into target selection by SCFFBXL17, a DQC E3 ligase that ubiquitylates and helps degrade inactive heterodimers of BTB proteins, while sparing functional homodimers. We find that SCFFBXL17 disrupts aberrant BTB dimers that fail to stabilize an intermolecular β-sheet around a highly divergent β-strand of the BTB domain. Complex dissociation allows SCFFBXL17 to wrap around a single BTB domain for robust ubiquitylation. SCFFBXL17 therefore probes both shape and complementarity of BTB domains, a mechanism that is well suited to establish quality control of complex composition for recurrent interaction modules.
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