Mehlen P, Briolay J, Smith L, Diaz-latoud C, Fabre N, Pauli D, Arrigo A P
Molecular and Cellular Genetics, CNRS UMR-106, Claude Bernard University, Lyon, France.
Eur J Biochem. 1993 Jul 15;215(2):277-84. doi: 10.1111/j.1432-1033.1993.tb18032.x.
The Drosophila melanogaster small heat-shock protein, hsp27 (Dhsp27) belongs to a family of polypeptides which shares a sequence related to alpha-crystallin and which protect cell against heat shock. Dhsp27 accumulates following heat shock and, in absence of stress, in the central nervous system, imaginal discs and the gonads of the developing fly. Two internal and adjacent deletion mutants in the conserved alpha-crystallin domain of Dhsp27 were constructed. Expression vectors containing either the coding sequence of Dhsp27 or that of the two deletion mutants linked to the Simian-Virus-40 late promoter were used to transfect monkey COS cells. The transient expression of Dhsp27 was found to decrease the sensitivity of COS cells to heat and hydrogen-peroxide stresses as judged by Trypan-blue staining and indirect immunofluorescence analysis. Using this rapid test, we observed that a deletion of 62 amino acids, which lies at the 5' end of the conserved alpha-crystallin domain and covers the first 41 amino acids of this region had only a weak effect on the protective activity of Dhsp27. This suggests that the N-terminal half of the conserved alpha-crystallin domain may not be essential for the protective activity of the small hsp. In contrast, Dhsp27 was no more active when the last 42 amino acids of the alpha-crystallin domain were deleted. Biochemical fractionation and indirect immunofluorescence analysis indicated that the protective function of Dhsp27 was localized at the level of the nucleus.
果蝇黑腹小热休克蛋白hsp27(Dhsp27)属于一类多肽家族,该家族与α-晶体蛋白具有相关序列,可保护细胞免受热休克。Dhsp27在热休克后积累,并且在无应激条件下,在发育中果蝇的中枢神经系统、成虫盘和性腺中积累。构建了Dhsp27保守α-晶体蛋白结构域中的两个内部相邻缺失突变体。含有Dhsp27编码序列或与猿猴病毒40晚期启动子相连的两个缺失突变体编码序列的表达载体用于转染猴COS细胞。通过台盼蓝染色和间接免疫荧光分析判断,发现Dhsp27的瞬时表达降低了COS细胞对热和过氧化氢应激的敏感性。使用这种快速测试,我们观察到位于保守α-晶体蛋白结构域5'端的62个氨基酸的缺失,覆盖该区域的前41个氨基酸,对Dhsp27的保护活性只有微弱影响。这表明保守α-晶体蛋白结构域的N端一半对于小热休克蛋白的保护活性可能不是必需的。相反,当α-晶体蛋白结构域的最后42个氨基酸缺失时,Dhsp27不再具有活性。生化分级分离和间接免疫荧光分析表明,Dhsp27的保护功能定位于细胞核水平。