The N-terminal 26-residue fragment of human programmed cell death 5 protein can form a stable α-helix having unique electrostatic potential character
The N-terminal 26-residue fragment of human programmed cell death 5 protein can form a stable α-helix having unique electrostatic potential character
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DOI：
10.1042/bj20050688
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发表时间：
2005-11-15
影响因子：
4.1
通讯作者：
Wang, JF
中科院分区：
文献类型：
--
作者：
Liu, DS;Yao, HW;Wang, JF
PDCD5-(1-26)是人PDCD5(程序性细胞死亡5)蛋白的N端26个残基片段。PDCD5是一种重要的新蛋白，它同时调节细胞的凋亡性和非凋亡性程序性死亡。PDCD5蛋白的构象是一个稳定的螺旋核心，由一个三螺旋束和两个解离的末端区域组成。N-末端区域是有序的，含有丰富的二级结构。为了更好地了解其三级结构，本研究对N末端26位氨基酸残基片段PDCD5(L 26)进行了高效表达和纯化。用圆二色谱、异核和同核核磁共振方法确定了PDCD5-(1-26)的Asp(3)-Ala(19)形成稳定的α-螺旋。PDCD5的N-末端残基Asp(3)-Ala(19)被证实具有独立于蛋白质核心形成稳定的α-螺旋的能力。对PDCD5-(1-26)螺旋肽的分析表明，这种结构良好的α-螺旋的表面具有独特的静电势特征。这可能为PDCD5的N-末端α-螺旋作为蛋白质的独立功能实体提供了环境。细胞凋亡活性分析表明，PDCD5 N端α-螺旋的缺失显著减弱了去血清对HL-60细胞的促凋亡作用。
PDCD5-(1-26) is a N-terminal 26-residue fragment of human PDCD5 (programmed cell death 5) protein. PDCD5 is an important novel protein that regulates both apoptotic and nonapoptotic programmed cell death. The conformation of PDCD5 protein is a stable helical core consisting of a triple-helix bundle and two dissociated terminal regions. The N-terminal region is ordered and contains abundant secondary structure. Overexpression and purification of the N-terminal 26-residure fragment, PDCD5-(l-26), was performed in this study to better understand its tertiary structure. The spectroscopic studies using CD and hetero- and homo-nuclear NMR methods determine a stable alpha-helix formed by Asp(3)-Ala(19) of PDCD5-(1-26). The N-terminal residues Asp(3)-Ala(19) of PDCD5 were then affirmed to have the capacity to form a stable alpha-helix independently of the core of the protein. Analysis of the helical peptide of PDCD5-(1-26) indicates that the surface of this well-formed alpha-helix has a unique electrostatic potential character. This may provide an environment for the N-terminal alpha-helix of PDCD5 to serve as an independent functional entity of the protein. The apoptosis activity assay shows that the deletion of the N-terminal alpha-helix of PDCD5 significantly attenuates the apoptosis-promoting effects on HL-60 cells induced by serum withdrawal.