Mao Xiang, Ren Zhiyong, Parker Gregory N, Sondermann Holger, Pastorello Michael A, Wang Wei, McMurray John S, Demeler Borries, Darnell James E, Chen Xiaomin
Department of Biochemistry and Molecular Biology, M.D. Anderson Cancer Center , The University of Texas, Houston, Texas 77030, USA.
Mol Cell. 2005 Mar 18;17(6):761-71. doi: 10.1016/j.molcel.2005.02.021.
The crystal structure has been determined at 3.0 A resolution for an unphosphorylated STAT1 (1-683) complexed with a phosphopeptide derived from the alpha chain of interferon gamma (IFNgamma) receptor. Two dimer interfaces are seen, one between the N domains (NDs) (amino acid residues 1-123) and the other between the core fragments (CFs) (residues 132-683). Analyses of the wild-type (wt) and mutant STAT1 proteins by static light scattering, analytical ultracentrifugation, and coimmunoprecipitation suggest that STAT1 is predominantly dimeric prior to activation, and the dimer is mediated by the ND interactions. The connecting region between the ND and the CF is flexible and allows two interconvertable orientations of the CFs, termed "antiparallel" or "parallel," as determined by SH2 domain orientations. Functional implications of these dimer conformations are discussed. Also revealed in this structure is the detailed interaction between STAT1 SH2 domain and its docking site on IFNgamma receptor.
已确定未磷酸化的STAT1（1-683）与源自干扰素γ（IFNγ）受体α链的磷酸肽形成的复合物在3.0埃分辨率下的晶体结构。观察到两个二聚体界面，一个在N结构域（NDs）（氨基酸残基1-123）之间，另一个在核心片段（CFs）（残基132-683）之间。通过静态光散射、分析超速离心和共免疫沉淀对野生型（wt）和突变型STAT1蛋白进行分析表明，STAT1在激活前主要以二聚体形式存在，且二聚体由ND相互作用介导。ND和CF之间的连接区域是灵活的，并且允许CFs有两种可相互转换的取向，根据SH2结构域的取向确定为“反平行”或“平行”。讨论了这些二聚体构象的功能意义。该结构还揭示了STAT1 SH2结构域与其在IFNγ受体上的对接位点之间的详细相互作用。
