在生物體中，去氧核醣核酸需要被纏繞保存，真核生物以組蛋白作為纏繞核酸的工具，在古生菌中，則有一群分子量7到10 KDa的蛋白質作類似的用途，稱之為「類組蛋白」蛋白質。Sso7c4是硫磺礦硫化葉菌中一個已知的「類組蛋白」蛋白質，本研究的目標蛋白質Saci_1212，則是Sso7c4在嗜酸熱硫化葉菌中的同源蛋白。在先前的研究中已經得知Sso7c4的C端序列(LKEPWK)，但正電且結構彈性，會參與去氧核醣核酸的作用。而有趣的是Saci_1212整體結構雖與Sso7c4相似，但C端蛋白質序列(TEEELR)卻帶有3個帶負電荷的麩胺酸殘基，與去氧核醣核酸的電性相排斥。
在本研究中，我們以X光蛋白質晶體繞射的技術得到解析度2.09 埃的Saci_1212蛋白質晶體結構。結構與Sso7c4相似，有著β-loop-β的結構為主體，這樣的折疊構型也與細菌的轉錄調控因子AbrB及 MazE之N端去氧核醣核酸結合區域的結構相似。在蛋白質結構的C端，Sso7c4是一個有彈性的手臂，沒有固定構型；Saci_1212則以三個麩胺酸殘基形成310¬-螺旋的結構，與Sso7c4完全不同。後續以電子顯微鏡拍攝Saci_1212原生型及C端刪除型兩種蛋白質分別以不同的比例與質體PhiX174 RF II DNA作用之影像。從影像分析，得知Saci_1212不同於Sso7c4，不會與去氧核醣核酸有架橋的作用；質體長度並無顯著縮短也顯示它不是一個彎曲者或纏繞者。與C端刪除型相比，原生型完全沒有架橋行為，C端刪除型則有局部架橋，顯示帶負電的C端序列會減少對DNA架橋效應的發生；又根據螢光極化分析的結果，Saci_1212之C端序列刪除後與去氧核醣核酸的結合力上升了20倍，顯示該C端序列降低了整體的結合力，但比較Saci_1212與同源蛋白質Sso7c4的C端刪除型，前者的結合力是後者的24倍，可能有與其他轉錄調控因子競爭去氧核醣核酸結合位的能力，故推測Saci_1212是一個基因轉錄的負調控因子。

Saci_1212 protein, a Sso7c4 homologue, is commonly believed to be a histone-like protein involved in genomic DNA compaction from Sulfolobus acidocaldarius. Although sequence alignments share high similarity (Saci_1212 vs Sso7c4: 66% identity), their C-termini are quite different in amino acid level. In previous study, we have been demonstrated that basic and flexible C-terminal ends of Sso7c4 (LKEPWK) are involved in binding and bending DNA whereas C-terminus of Saci_1212 (TEEELR) contains three glutamate residues which disfavor to interact with DNA due to the negative charge repulsions.
Here, to obtain a detailed understanding of its architectural properties, we present the crystal structure of wild type Saci_1212 at 2.09 Å resolution. The overall structure of Saci_1212 is similar to Sso7c4 which forms a swapped β-loop-β ′Yin-Yang′ topology. This fold resembles the N-terminal DNA-binding domain of both AbrB and MazE, which are transcriptional regulators in bacteria. The two basic C-termini of Sso7c4 are disordered owing to a lack of corresponding density in the crystal. However, the two C-termini of Saci_1212 adopt the 310-helical conformation by three glutamate residues. Two C-termini of Saci_1212 are quite different from that of Sso7c4 either in amino acid sequence or secondary structure. In fluorescence polarization binding assays, C-terminally truncated proteins exhibited higher binding affinity to 20-bp DNA than the wild-type protein to approximately 20-fold. These FP data further show that the C-terminal ends of Saci_1212 decrease the interaction with DNA. As shown in electron microscopy (EM) images, wild-type Sso7c4 compacts DNA through bridging and bending interactions, whereas the Saci_1212 protein binds DNA without any bridging phenomenon and no compaction of the DNA occurs. A functional role for Saci_1212 as negative transcriptional regulator is suggested.

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