Département de Biochimie et Médicine Moléculaire, Université de Montréal, C.P. 6128 Succursale Centre-Ville, Montréal, QC H3C 3J7, Canada.
Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan.
Structure. 2020 May 5;28(5):573-585.e5. doi: 10.1016/j.str.2020.04.002. Epub 2020 Apr 28.
The human PIAS proteins are small ubiquitin-like modifier (SUMO) E3 ligases that participate in important cellular functions. Several of these functions depend on a conserved SUMO-interacting motif (SIM) located in the central region of all PIAS proteins (SIM1). Recently, it was determined that Siz2, a yeast homolog of PIAS proteins, possesses a second SIM at its C terminus (SIM2). Sequence alignment indicates that a SIM2 is also present in PIAS1-3, but not PIAS4. Using biochemical and structural studies, we demonstrate PIAS-SIM2 binds to SUMO1, but that phosphorylation of the PIAS-SIM2 or acetylation of SUMO1 alter this interaction in a manner distinct from what is observed for the PIAS-SIM1. We also show that the PIAS-SIM2 plays a key role in formation of a UBC9-PIAS1-SUMO1 complex. These results provide insights into how post-translational modifications selectively regulate the specificity of multiple SIMs found in the PIAS proteins by exploiting the plasticity built into the SUMO-SIM binding interface.
人类 PIAS 蛋白是小泛素样修饰物 (SUMO) E3 连接酶，参与重要的细胞功能。这些功能中的几个依赖于所有 PIAS 蛋白（SIM1）中央区域的保守 SUMO 相互作用基序 (SIM)。最近，确定酵母 PIAS 蛋白的同源物 Siz2 在其 C 末端（SIM2）具有第二个 SIM。序列比对表明，SIM2 也存在于 PIAS1-3 中，但不存在于 PIAS4 中。使用生化和结构研究，我们证明 PIAS-SIM2 与 SUMO1 结合，但 PIAS-SIM2 的磷酸化或 SUMO1 的乙酰化以不同于观察到的 PIAS-SIM1 的方式改变这种相互作用。我们还表明，PIAS-SIM2 在 UBC9-PIAS1-SUMO1 复合物的形成中起关键作用。这些结果提供了关于如何通过利用 SUMO-SIM 结合界面中的可塑性来选择性调节 PIAS 蛋白中多个 SIM 的特异性的见解。
