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Structural basis for dimerization quality control

机译：二元质量控制的结构基础

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摘要

Most quality control pathways target misfolded proteins to prevent toxic aggregation and neurodegeneration(1). Dimerization quality control further improves proteostasis by eliminating complexes of aberrant composition(2), but how it detects incorrect subunits remains unknown. Here we provide structural insight into target selection by SCF-FBXL17, a dimerization-quality-control E3 ligase that ubiquitylates and helps to degrade inactive heterodimers of BTB proteins while sparing functional homodimers. We find that SCF-FBXL17 disrupts aberrant BTB dimers that fail to stabilize an intermolecular beta-sheet around a highly divergent beta-strand of the BTB domain. Complex dissociation allows SCF-FBXL17 to wrap around a single BTB domain, resulting in robust ubiquitylation. SCF-FBXL17 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.Structural studies of the dimerization quality control E3 ubiquitin ligase SCF-FBXL17 indicate that its selectivity for aberrant complex formation is based on recognizing both shape and complementarity of interacting domains.
机译：大多数质量控制途径靶被错误折叠的蛋白质，以防止有毒聚集和神经变性（1）。二聚化质量控制进一步通过消除异常组成的复合物（2）来改善蛋白质，但是如何检测到不正确的亚基仍然未知。在这里，我们通过SCF-FBX117提供对目标选择的结构洞察，其泛化质量控制E3连接酶，其ubiquitylate，并且有助于降解BTB蛋白的惰性异二聚体，同时保留官能偶联剂。我们发现SCF-FBXL17破坏了不稳定在BTB结构域的高度发散的β-股围绕分子间β-片的异常BTB二聚体。复杂解离允许SCF-FBXL17包围单个BTB域，导致稳健的泛曲。因此，SCF-FBX117探测BTB结构域的形状和互补性，该机制非常适合于建立复杂组合物的质量控制，用于复发相互作用模块。二聚化质量控制E3的结构研究表明其对异常的选择性复杂的形成基于识别相互作用域的形状和互补性。

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  • 来源
    《Nature》 |2020年第7829期|452-456|共5页
  • 作者

    Mena Elijah L.; Jevtic Predrag; Greber Basil J.; Gee Christine L.; Lew Brandon G.; Akopian David; Nogales Eva; Kuriyan John; Rape Michael;

  • 作者单位

    Univ Calif Berkeley Dept Mol & Cell Biol 229 Stanley Hall Berkeley CA 94720 USA|Harvard Med Sch Dept Genet Boston MA 02115 USA;

    Univ Calif Berkeley Dept Mol & Cell Biol 229 Stanley Hall Berkeley CA 94720 USA|Univ Calif Berkeley Howard Hughes Med Inst Berkeley CA 94720 USA;

    Univ Calif Berkeley Calif Inst Quantitat Biosci QB3 Berkeley CA 94720 USA|Lawrence Berkeley Natl Lab Mol Biophys & Integrat Bioimaging Div Berkeley CA USA;

    Univ Calif Berkeley Dept Mol & Cell Biol 229 Stanley Hall Berkeley CA 94720 USA|Univ Calif Berkeley Howard Hughes Med Inst Berkeley CA 94720 USA;

    Univ Calif Berkeley Dept Mol & Cell Biol 229 Stanley Hall Berkeley CA 94720 USA|Univ Calif Berkeley Howard Hughes Med Inst Berkeley CA 94720 USA;

    Univ Calif Berkeley Dept Mol & Cell Biol 229 Stanley Hall Berkeley CA 94720 USA;

    Univ Calif Berkeley Dept Mol & Cell Biol 229 Stanley Hall Berkeley CA 94720 USA|Univ Calif Berkeley Howard Hughes Med Inst Berkeley CA 94720 USA|Univ Calif Berkeley Calif Inst Quantitat Biosci QB3 Berkeley CA 94720 USA|Lawrence Berkeley Natl Lab Mol Biophys & Integrat Bioimaging Div Berkeley CA USA;

    Univ Calif Berkeley Dept Mol & Cell Biol 229 Stanley Hall Berkeley CA 94720 USA|Univ Calif Berkeley Howard Hughes Med Inst Berkeley CA 94720 USA|Univ Calif Berkeley Calif Inst Quantitat Biosci QB3 Berkeley CA 94720 USA|Lawrence Berkeley Natl Lab Mol Biophys & Integrat Bioimaging Div Berkeley CA USA|Univ Calif Berkeley Dept Chem Berkeley CA 94720 USA;

    Univ Calif Berkeley Dept Mol & Cell Biol 229 Stanley Hall Berkeley CA 94720 USA|Univ Calif Berkeley Howard Hughes Med Inst Berkeley CA 94720 USA|Univ Calif Berkeley Calif Inst Quantitat Biosci QB3 Berkeley CA 94720 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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