最近，TAR DNA-binding protein-43 (TDP-43)蛋白已被發現在許多神經疾病裡扮演著重要的角色，例如：額顳葉退化症(FTLD)和漸凍人症(ALS)。為了更深入的討論這個蛋白質的性質，我們試著去表現不同長度的TDP蛋白質，其中有TDPFL、TDP1-265、TDP1-207及TDP106-265。這些蛋白皆利用大腸桿菌E.coli BL21(DE3)表現，然後再以鎳離子管柱做純化並且跑SDS PAGE確認物種。經由化學交聯反應與膠體管柱層析方法，我們鑑別出不同長度的TDP-43蛋白形成寡聚（oligomerization）的能力不同。根據膠體管柱層析初步的結果，我們發現TDPFL會形成三聚體（trimer）及六聚體（hexamer），而TDP1-265及TDP1-207的主要構型是單體及二聚體。此外，TDP106-265是以單體存在著。經由化學交聯實驗與Native PAGE結果，我們也可以發現TDPFL、TDP1-265及 TDP1-207有oligomerization的現象，但是TDP106-265則沒有發生oligomer。這指出N端極為可能是扮演著oligomerization與聚集化現象的重要角色。同時，在實驗室同仁的協助下，我們也利用圓二色光譜（circular dichroism）去探討蛋白的構型變化。結果指出，TDP1-265及TDP1-207含有很高成分的Random coil，其次，也可看出有α-helix與β-sheet的結構，TDP106-265則主要是α-helix和β-sheet。在與ss(TG)6DNA結合之後，可以發現TDP1-265比TDP106-265有顯著的Random coil變化，這個發現暗示了N端在結合DNA上扮演重要的角色。在未來後續發展上，可以提供一個新的參考在TDP-43蛋白的研究上。

Recently, TAR DNA-binding protein-43 (TDP-43) has been found to play an important role in many neurodegenerative disease, such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). In this study, we have tried to synthesize the TDP-43 of different length, including TDPFL, TDP1-265, TDP1-207, TDP106-265. All proteins are expressed in E.coli BL21(DE3), purified by Ni column and identified on the SDS PAGE. Via two experiments, cross-linking and gel filtration, we have characterized the conformations of these recombinant TDP-43. According to our preliminary Gel filtration chromatography results, we have found that TDPFL forms trimer and hexamer, and the major forms of TDP1-265 and TDP1-207 were monomer and dimer. In contrast, TDP106-265 was mainly monomer. By cross-linking experiments, we could see oligomers on TDPFL, TDP1-265 and TDP1-207, but not on TDP106-265, indicating that N-terminal probably plays an important role in the oligomerization and aggregation. Meanwhile, we used circular dichroism to study protein conformational changes. The results showed that TDP1-265 and TDP1-207 had high percentage of random coil structure. Also, α-helix and β-sheet structures were found. Besides, TDP106-265 was mainly α-helix and anti-parallel β-sheet. After binding with ss (TG) 6DNA, it was found that random coil of TDP1-265 changed significantly more than that of TDP106-265, which as far as we know was the first study to discover the role of N-terminal on DNA binding. Our new findings can shed light on future TDP-43 protein research.

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