NF-κB 是一個重要的轉錄因子並參與了許多細胞反應像是細胞活化、細胞生存、增生、發炎以及免疫反應。在對應的受體接收到刺激活化後，訊息會傳遞到一個包含了CARMA 家族的蛋白、BCL10 以及MALT1 的CBM 複合體來促使下游的NF-κB 活化。當它失調的時候會導致NF-κB持續性活化或是抑制進而導致免疫缺陷疾病的產生。然而，CBM 複合體形成的詳細機制仍未被解析。在我們的研究中，我們解出了MALT1 death domain 的晶體結構，解析度高達2.1 Å。其中，解析出了兩段之前未解析的區域。這兩段區域參與了MALT1 的C 端螺旋的結構穩定。與之前解析出的結構比較，在C 端螺旋處我們認為和NLRP14 的PYD 形成stemhelix的dimer 相似，這兩個蛋白在水溶液中同時存在monomer 與dimer。並在C 端螺旋處可以找到兩者相似的氨基酸去調控構形。比對之前的BCL10-MALT1 結構中，我們發現MALT1 是藉由一個N+7 的規則去產生交互作用。這樣的dimerization 能獲得重要的蛋白水解的活性來參與NF-κB 的訊息傳遞。此外，我們證明了 immunoglobin domain 2 也對於MALT1形成oligomer 是另外一條重要的途徑。另一方面，我們發現BCL10 和MALT1 有兩個不同的接觸區域。綜合來說，這些結果幫助我們闡述了CBM 複合體的組成以及他們如何調控下游的訊息傳遞路線。

Nuclear factor κB (NF-κB) is a crucial transcription factor to regulate lots of signaling pathway in our human body. It participates in lots of cellular responses such as cell activation, cell survival, proliferation, inflammation, and immune response. After activation of the corresponding receptors, signaling cascade transduction into a ternary complex which composed by CARMA family proteins, BCL10 and MALT1 and eventually activate the NF-κB. This complex is called CBM complex which dysregulation could lead to NF-κB constitutive activation or inhibition and cause lots of immunodeficiency diseases. However, the detail mechanism of CBM complex formation still unclear. In our research, we solved the crystal structure of the MALT1 death domain at a resolution of 2.1 Å. We identify two flexible loop that did not solved in previous structure. These loops participate the stabilization of MALT1 helix in the C-terminus. Compared to the previous structures, the C-terminus helix of MALT1 has a conformational difference. We propose that MALT1 is similar to the NLRP14 PYD to form a stem-helix mediated dimer. Both NLRP14 PYD and MALT1 forms monomer and dimer in the solution. There is a conformational regulation element in the NLRP14 PYD which can correspond to H115, E50 and M113 in MALT1 DD. Otherwise, fit MALT1 IG domain in the BCL10-MALT1 cryo-EM structure shows that MALT1 has large distance and angle to the other MALT1. Interestingly, we found a N to N+7 rule that MALT1 may interact with each other to form a dimer. MALT1 dimerization is important for its proteolytic activity to participate in the NF-κB signaling pathway. In addition, we proof that the immunoglobin domain 2 of MALT1 is crucial to interact with immunoglobin domain 1 to form the oligomer. Otherwise, we found two different interactions between BCL10 and MALT1. Taken together, these results help us to elucidate how the CBM complex assembles and regulates the downstream signaling pathway.

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