肿瘤抑制因子p53寡聚化结构域的精细溶液结构

Refined solution structure of the oligomerization domain of the tumour suppressor p53.

作者信息

Clore G M, Ernst J, Clubb R, Omichinski J G, Kennedy W M, Sakaguchi K, Appella E, Gronenborn A M

机构信息

Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.

出版信息

Nat Struct Biol. 1995 Apr;2(4):321-33. doi: 10.1038/nsb0495-321.

DOI:10.1038/nsb0495-321

PMID:7796267

Abstract

The NMR solution structure of the oligomerization domain of the tumour suppressor p53 (residues 319-360) has been refined. The structure comprises a dimer of dimers, oriented in an approximately orthogonal manner. The present structure determination is based on 4,472 experimental NMR restraints which represents a three and half fold increase over our previous work in the number of NOE restraints at the tetramerization interface. A comparison with the recently solved 1.7 A resolution X-ray structure shows that the structures are very similar and that the average angular root-mean-square difference in the interhelical angles is about 1 degree. The results of recent extensive mutagenesis data and the possible effects of mutations which have been identified in human cancers are discussed in the light of the present structure.

摘要

肿瘤抑制因子p53寡聚化结构域（第319 - 360位氨基酸残基）的核磁共振（NMR）溶液结构已得到优化。该结构由两个二聚体组成，它们以近似正交的方式排列。目前的结构测定基于4472个实验性NMR约束条件，这比我们之前在四聚化界面处的NOE约束数量的工作增加了三倍半。与最近解析出的1.7埃分辨率的X射线结构相比，结果表明这两种结构非常相似，螺旋间角度的平均角均方根差异约为1度。结合当前结构，讨论了近期广泛的诱变数据结果以及在人类癌症中已鉴定出的突变可能产生的影响。