Jeffrey P D, Gorina S, Pavletich N P
Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021.
Science. 1995 Mar 10;267(5203):1498-502. doi: 10.1126/science.7878469.
The p53 protein is a tetrameric transcription factor that plays a central role in the prevention of neoplastic transformation. Oligomerization appears to be essential for the tumor suppressing activity of p53 because oligomerization-deficient p53 mutants cannot suppress the growth of carcinoma cell lines. The crystal structure of the tetramerization domain of p53 (residues 325 to 356) was determined at 1.7 angstrom resolution and refined to a crystallographic R factor of 19.2 percent. The monomer, which consists of a beta strand and an alpha helix, associates with a second monomer across an antiparallel beta sheet and an antiparallel helix-helix interface to form a dimer. Two of these dimers associate across a second and distinct parallel helix-helix interface to form the tetramer.
p53蛋白是一种四聚体转录因子，在预防肿瘤转化中起核心作用。寡聚化似乎对p53的肿瘤抑制活性至关重要，因为缺乏寡聚化的p53突变体无法抑制癌细胞系的生长。p53四聚化结构域（第325至356位氨基酸残基）的晶体结构在1.7埃分辨率下测定，并精修至晶体学R因子为19.2%。该单体由一条β链和一条α螺旋组成，通过一个反平行β折叠和一个反平行螺旋-螺旋界面与第二个单体缔合形成二聚体。其中两个二聚体通过第二个不同的平行螺旋-螺旋界面缔合形成四聚体。
