Binding of SGTA to Rpn13 selectively modulates protein quality control.
Binding of SGTA to Rpn13 selectively modulates protein quality control.
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SGTA与RPN13的结合选择性调节蛋白质质量控制。
DOI：
10.1242/jcs.165209
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发表时间：
2015-09-01
影响因子：
4
通讯作者：
High S
中科院分区：
文献类型：
--
作者：
Leznicki P;Korac-Prlic J;Kliza K;Husnjak K;Nyathi Y;Dikic I;High S
Rpn 13是26 S蛋白酶体调节亚基的内在泛素受体，其在降解之前促进底物捕获。在这里，我们表明，Rpn 13的C-末端区域结合的tetratricopeptide重复（TPR）结构域的SGTA，一个细胞溶质因子牵连在质量控制的错误定位的膜蛋白（MLP）。SGTA的过表达导致稳态MLP水平的大幅增加，这与对蛋白酶体降解的影响一致。然而，这种作用强烈依赖于SGTA与蛋白酶体组分Rpn 13的相互作用。因此，Rpn 13的SGTA结合区的过表达或SGTA TPR结构域内的点突变均抑制SGTA与蛋白酶体的结合并显著降低MLP水平。这些发现表明，SGTA可以调节MLP进入蛋白酶体的蛋白水解核心，这意味着涉及SGTA和BAG 6复合物的蛋白质质量控制循环可以在19 S调节颗粒处操作。我们推测SGTA与Rpn 13的结合使特定多肽能够逃避蛋白酶体降解和/或选择性地调节底物降解。突出显示的文章：SGTA与蛋白酶体的结合延迟了底物降解，从而提供了一种拯救潜在活性蛋白以供重复使用的机制。
Rpn13 is an intrinsic ubiquitin receptor of the 26S proteasome regulatory subunit that facilitates substrate capture prior to degradation. Here we show that the C-terminal region of Rpn13 binds to the tetratricopeptide repeat (TPR) domain of SGTA, a cytosolic factor implicated in the quality control of mislocalised membrane proteins (MLPs). The overexpression of SGTA results in a substantial increase in steady-state MLP levels, consistent with an effect on proteasomal degradation. However, this effect is strongly dependent upon the interaction of SGTA with the proteasomal component Rpn13. Hence, overexpression of the SGTA-binding region of Rpn13 or point mutations within the SGTA TPR domain both inhibit SGTA binding to the proteasome and substantially reduce MLP levels. These findings suggest that SGTA can regulate the access of MLPs to the proteolytic core of the proteasome, implying that a protein quality control cycle that involves SGTA and the BAG6 complex can operate at the 19S regulatory particle. We speculate that the binding of SGTA to Rpn13 enables specific polypeptides to escape proteasomal degradation and/or selectively modulates substrate degradation. Highlighted Article: Binding of SGTA to the proteasome delays substrate degradation, thereby providing a mechanism for potentially viable proteins to be rescued for reuse.