p53的寡聚化结构域：三角形式的晶体结构

The oligomerization domain of p53: crystal structure of the trigonal form.

作者信息

Miller M, Lubkowski J, Rao J K, Danishefsky A T, Omichinski J G, Sakaguchi K, Sakamoto H, Appella E, Gronenborn A M, Clore G M

机构信息

Macromolecular Structure Laboratory, NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, Frederick, MD 21702, USA.

出版信息

FEBS Lett. 1996 Dec 9;399(1-2):166-70. doi: 10.1016/s0014-5793(96)01231-8.

DOI:10.1016/s0014-5793(96)01231-8

PMID:8980144

Abstract

The structure of the oligomerization domain of the p53 tumor suppressor protein was determined in the trigonal crystal form, using a refined NMR structure as a model. A synthetic peptide comprising residues 319-360 of human p53 crystallized in the space group P3(1)21. There is one biologically relevant tetrameric domain in the crystallographic asymmetric unit. The structure was refined jointly with NMR data, only the third such case (the previous examples being IL-1beta (Shaanan, B., Gronenborn, A.M., Cohen, G.H., Gilliland, G.L., Veerapandian, B., Davies, D.R. and Clore, G.M. (1992) Science 257, 961-964 [1]) and BPTI (Schiffer, C., Huber, R., Wuthrich, K. and Van Gunsteren, W.F. (1994) J. Mol. Biol. 241, 588-599 [21)), to 2.5 A resolution with an R factor of 0.207. The distribution of tumor-derived mutations in the oligomerization region together with structural and biological data suggest a strategy for the design of antitumor therapeutics.

摘要

以优化后的核磁共振结构为模型，确定了p53肿瘤抑制蛋白寡聚化结构域在三角晶体形式下的结构。一条包含人p53第319 - 360位残基的合成肽在空间群P3(1)21中结晶。在晶体学不对称单元中有一个生物学相关的四聚体结构域。该结构与核磁共振数据联合优化，这是仅有的第三例（前两例分别是白细胞介素-1β（Shaanan, B., Gronenborn, A.M., Cohen, G.H., Gilliland, G.L., Veerapandian, B., Davies, D.R. 和Clore, G.M. (1992) Science 257, 961 - 964 [1]）和抑肽酶（Schiffer, C., Huber, R., Wuthrich, K. 和Van Gunsteren, W.F. (1994) J. Mol. Biol. 241, 588 - 599 [21]）），分辨率达到2.5 Å，R因子为0.207。寡聚化区域中肿瘤来源突变的分布以及结构和生物学数据提示了一种抗肿瘤治疗药物的设计策略。