Institute of Biochemistry, University of Cologne, Cologne, Germany.
Max Planck Institute for Plant Breeding Research, Cologne, Germany.
Nat Commun. 2023 Aug 15;14(1):4925. doi: 10.1038/s41467-023-40447-y.
Proteins from the signal transduction ATPases with numerous domains (STAND) family are known to play an important role in innate immunity. However, it remains less well understood how they function in transcriptional regulation. MalT is a bacterial STAND that controls the Escherichia coli maltose system. Inactive MalT is sequestered by different inhibitory proteins such as MalY. Here, we show that MalY interacts with one oligomerization interface of MalT to form a 2:2 complex. MalY represses MalT activity by blocking its oligomerization and strengthening ADP-mediated MalT autoinhibition. A loop region N-terminal to the nucleotide-binding domain (NBD) of MalT has a dual role in mediating MalT autoinhibition and activation. Structural comparison shows that ligand-binding induced oligomerization is required for stabilizing the C-terminal domains and conferring DNA-binding activity. Together, our study reveals the mechanism whereby a prokaryotic STAND is inhibited by a repressor protein and offers insights into signaling by STAND transcription activators.
具有众多结构域的信号转导 ATP 酶（STAND）家族的蛋白质在先天免疫中起着重要作用。然而，它们在转录调控中的作用仍不太清楚。MalT 是一种细菌 STAND，它控制大肠杆菌麦芽糖系统。失活的 MalT 被不同的抑制蛋白如 MalY 隔离。在这里，我们表明 MalY 与 MalT 的一个寡聚化界面相互作用，形成 2:2 复合物。MalY 通过阻止 MalT 的寡聚化和增强 ADP 介导的 MalT 自动抑制来抑制 MalT 活性。MalT 的核苷酸结合结构域（NBD）N 端的一个环区在介导 MalT 自动抑制和激活方面具有双重作用。结构比较表明，配体结合诱导的寡聚化对于稳定 C 末端结构域和赋予 DNA 结合活性是必需的。总之，我们的研究揭示了一种原核 STAND 如何被抑制蛋白抑制的机制，并为 STAND 转录激活因子的信号转导提供了深入的了解。
