Clore G M, Omichinski J G, Sakaguchi K, Zambrano N, Sakamoto H, Appella E, Gronenborn A M
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892.
Science. 1994 Jul 15;265(5170):386-91. doi: 10.1126/science.8023159.
The three-dimensional structure of the oligomerization domain (residues 319 to 360) of the tumor suppressor p53 has been solved by multidimensional heteronuclear magnetic resonance (NMR) spectroscopy. The domain forms a 20-kilodalton symmetric tetramer with a topology made up from a dimer of dimers. The two primary dimers each comprise two antiparallel helices linked by an antiparallel beta sheet. One beta strand and one helix are contributed from each monomer. The interface between the two dimers forming the tetramer is mediated solely by helix-helix contacts. The overall result is a symmetric, four-helix bundle with adjacent helices oriented antiparallel to each other and with the two antiparallel beta sheets located on opposing faces of the molecule. The tetramer is stabilized not only by hydrophobic interactions within the protein core but also by a number of electrostatic interactions. The implications of the structure of the tetramer for the biological function of p53 are discussed.
肿瘤抑制蛋白p53寡聚化结构域（第319至360位氨基酸残基）的三维结构已通过多维异核磁共振（NMR）光谱解析。该结构域形成一个20千道尔顿的对称四聚体，其拓扑结构由两个二聚体组成。两个主要的二聚体各由两条反平行螺旋通过一条反平行β折叠连接而成。每条单体贡献一条β链和一条螺旋。形成四聚体的两个二聚体之间的界面仅由螺旋-螺旋接触介导。总体结果是形成一个对称的四螺旋束，相邻螺旋彼此反平行，两条反平行β折叠位于分子的相对面上。四聚体不仅通过蛋白质核心内的疏水相互作用得以稳定，还通过一些静电相互作用得以稳定。文中讨论了四聚体结构对p53生物学功能的影响。
