Structural studies of the NOD module of the transcriptional activator MalT in complex with its regulatory proteins MalK, MalY, and Aes

MalT是大肠杆菌中麦芽糖调控的全局转录激活因子。它属于新发现的具有众多结构域的信号转导ATP酶（STAND），类似于一个复杂的调节开关，通过与细胞质蛋白MalK、MalY和Aes的相互作用来响应ATP和麦芽糖糖等正信号和负信号。MalK， MalY和Aes的结构已经确定，但它们的相互作用位点，MalT的核苷酸结合寡聚结构域（NOD）以及它们相互作用的分子细节仍有待阐明。我们的目标是为MalT的NOD模块及其与负效应物MalK、MalY和Aes的相互作用提供结构和功能上的见解。为此，将研究不同的MalT片段与MalK、MalY或Aes形成配合物的能力。我们还将尝试共结晶所得到的配合物，并确定其x射线结构。这些研究有望为MalT调控中涉及的信号传导过程提供详细的结构视图，并将有助于我们了解STAND蛋白的信号传导。

MalT is the global transcriptional activator of the maltose regulon in E. coli. It belongs to the newly recognized class of Signal Transduction ATPases with Numerous Domains (STAND), resembling a complex regulatory switch that responds to positive signals, such as ATP and maltotriose, as well as negative signals, mediated by the interaction with the cytoplasmic proteins MalK, MalY, and Aes. The structures of MalK, MalY and Aes have been determined, but their interaction site, the Nucleotide-binding-Oligomerization Domain (NOD) of MalT, as well as the molecular details of their interactions remain to be elucidated. We aim to provide structural and functional insights into the NOD module of MalT and its interactions with the negative effectors MalK, MalY, and Aes. To this end, different MalT fragments will be investigated for their ability to form complexes with MalK, MalY, or Aes. We will also attempt to co-crystallize the resulting complexes and to determine their X-ray structures. These studies are expected to provide a detailed structural view of the signaling processes involved in MalT regulation and will contribute to our understanding of the signaling by STAND proteins in general.