The SDS22:PP1:I3 complex: SDS22 binding to PP1 loosens the active site metal to prime metal exchange.
The SDS22:PP1:I3 complex: SDS22 binding to PP1 loosens the active site metal to prime metal exchange.
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DOI：
10.1016/j.jbc.2023.105515
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发表时间：
2024-01
影响因子：
4.8
通讯作者：
Peti, Wolfgang
中科院分区：
文献类型：
--
作者：
Choy, Meng S;Srivastava, Gautam;Robinson, Lucy C;Tatchell, Kelly;Page, Rebecca;Peti, Wolfgang
SDS22和Inhibitor-3 （I3）是两个古老的蛋白磷酸酶1 （PP1）调节剂，调节多种重要的生物过程。SDS22和I3与PP1形成稳定的二聚体配合物；然而，对于PP1调节因子来说，它们也形成三重复合物，其中两种蛋白同时与PP1结合（SPI复合物）。在这里，我们报告了SPI配合物的晶体结构。虽然这两种调节因子结合PP1的构象与在它们各自的PP1复合物中观察到的构象相同，但PP1采用sds22结合的构象，缺乏M1金属。出乎意料的是，表面等离子体共振（SPR）显示I3对SDS22:PP1复合物的亲和力比单独PP1低约10倍。我们发现这种结合亲和力的变化仅仅是由于I3与PP1活性位点的相互作用，特别是PP1的M2金属，这表明SDS22可能允许PP1 M2金属交换，从而实现PP1的生物发生。
SDS22 and Inhibitor-3 (I3) are two ancient regulators of protein phosphatase 1 (PP1) that regulate multiple essential biological processes. Both SDS22 and I3 form stable dimeric complexes with PP1; however, and atypically for PP1 regulators, they also form a triple complex, where both proteins bind to PP1 simultaneously (SPI complex). Here we report the crystal structure of the SPI complex. While both regulators bind PP1 in conformations identical to those observed in their individual PP1 complexes, PP1 adopts the SDS22-bound conformation, which lacks its M1 metal. Unexpectedly, surface plasmon resonance (SPR) revealed that the affinity of I3 for the SDS22:PP1 complex is ∼10-fold lower than PP1 alone. We show that this change in binding affinity is solely due to the interaction of I3 with the PP1 active site, specifically PP1’s M2 metal, demonstrating that SDS22 likely allows for PP1 M2 metal exchange and thus PP1 biogenesis.