Structural Analysis of TCL-1 and MTCP-1 Proteins

TCL-1 和 MTCP-1 蛋白的结构分析

• 批准号: 6340779
• 负责人: Irene T Weber
• 金额: $ 25.85万
• 依托单位: THOMAS JEFFERSON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-05-01 至 2001-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6340779
• 关键词: B lymphocyte; T lymphocyte; X ray crystallography; chronic lymphocytic leukemia; circular dichroism; mutant; nuclear magnetic resonance spectroscopy; oncogenes; oncoproteins; protein purification; protein structure function; site directed mutagenesis; tumor suppressor proteins

TCL-1 and MTCP-1 are members of a novel family of human genes that are involved in T-ell malignancies and lymphoid proliferation and/or survival. These genes code for proteins of about 14 kDa molecular weight, that share 41% identical amino acid residues. Human TCL-1 and MTCP-1 and mouse TCL-1 have been expressed in E. coli and purified in milligram quantities for structural analysis. The crystal structure of MTCP-1 has been determined at 2.0 A resolution. The structure is a unique 8-stranded beta barrel with one short helix. The structure of TCL- 1 is very similar with a root mean square deviation of 1.7 angstrom on all common Calpha atoms. The structural information is being used for site- directed mutagenesis, and to design peptide analogs of surface regions of the proteins as potential inhibitors of oncogene function. Mutant forms of TCL-1 and MTCP-1 will be expressed, characterized and analyzed structurally in comparison to the wild type protein. Interacting proteins and other potential ligands of TCL-1 and MTCP-1 will be studied by crystallography and biochemical methods. The structures and functions of TCL-1 and MTP-1 proteins will be compared. Inhibitors of TCL-1 and MTCP-1 have potential for treatment for low-grade T-cell lymphomas and leukemias.

TCL-1 和 MTCP-1 是涉及 T 细胞恶性肿瘤和淋巴增殖和/或存活的新型人类基因家族的成员。这些基因编码分子量约为 14 kDa 的蛋白质，具有 41% 相同的氨基酸残基。人 TCL-1 和 MTCP-1 以及小鼠 TCL-1 已在大肠杆菌中表达，并以毫克级纯化用于结构分析。 MTCP-1 的晶体结构已在 2.0 A 分辨率下确定。该结构是一种独特的 8 股 β 桶，带有一个短螺旋。 TCL-1的结构非常相似，所有常见Cα原子的均方根偏差为1.7埃。结构信息被用于定点诱变，并设计蛋白质表面区域的肽类似物作为癌基因功能的潜在抑制剂。 TCL-1 和 MTCP-1 的突变形式将与野生型蛋白进行表达、表征和结构分析。将通过晶体学和生化方法研究 TCL-1 和 MTCP-1 的相互作用蛋白和其他潜在配体。将比较TCL-1和MTP-1蛋白的结构和功能。 TCL-1 和 MTCP-1 抑制剂具有治疗低度 T 细胞淋巴瘤和白血病的潜力。