CRYSTALLOGRAPHIC STUDIES OF DNA REPLICATION & CELLULAR SIGNALING: ONCOGENE

DNA 复制的晶体学研究

• 批准号: 6339143
• 负责人: JOHN KURIYAN
• 金额: $ 6.49万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-15 至 2001-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6339143
• 关键词: bioimaging /biomedical imaging; biological products; biomedical resource; proteins; radiography; structural biology

The crystal structure of the DNA complex of a STAT-1 homodimer has been determined at 2.9
resolution. STAT-1 utilizes a DNA binding domain with an immunoglobulin fold, similar to that of NFkB and the p53 tumor suppressor protein. The STAT-1 dimer forms a contiguous C-shaped clamp around DNA that is stabilized by reciprocal and highly specific interactions between the SH2 domain of one monomer and the C-terminal segment, phosphorylated on tyrosine, of the other. The phosphotyrosine binding site of the SH2 domain in each monomer is coupled structurally to the DNA binding domain, suggesting a potential role for the SH2-phosphotyrosine interaction in the stabilization of DNA interacting elements.

STAT-1 同二聚体 DNA 复合物的晶体结构具有 分辨率为2.9。 STAT-1 利用 DNA 结合 具有免疫球蛋白折叠的结构域，类似于 NFkB 和 p53 肿瘤抑制蛋白。 STAT-1二聚体形成连续的 DNA 周围的 C 形夹，通过相互和高度稳定而稳定 一个单体的 SH2 结构域与 另一个的 C 末端片段，在酪氨酸上磷酸化。 这 每个单体中SH2结构域的磷酸酪氨酸结合位点是 与 DNA 结合域结构耦合，表明潜在的 SH2-磷酸酪氨酸相互作用在稳定性中的作用 DNA 相互作用元件。