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

麦芽是大肠杆菌中麦芽糖调节子的全球转录激活剂。它属于新发现的一类具有多个结构域的信号转导ATPase，类似于一个复杂的调节开关，通过与细胞质蛋白Malk、Maly和AES的相互作用来响应积极的信号，如ATP和麦芽三糖，以及消极的信号。Malk、Maly和AES的结构已经确定，但它们的相互作用部位、麦芽的核苷酸结合寡聚化结构域(NOD)以及它们相互作用的分子细节仍有待阐明。我们的目标是提供对麦芽的NOD模块的结构和功能的见解，以及它与负效应因子Malk、Maly和AES的相互作用。为此，将研究不同的麦芽碎片与麦芽、苹果酸或AES形成络合物的能力。我们还将尝试将生成的络合物共结晶并确定它们的X射线结构。这些研究有望提供参与MALT调控的信号过程的详细结构图，并有助于我们从总体上理解标准蛋白的信号转导。

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.