视网母细胞瘤瘤抑制器口袋域的结构与HPV E7的酸结合在一起
J O Lee1, A A Russo, N P Pavletich
1Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Nature
|March 12, 1998
概括
视网膜母细胞瘤 (Rb) 瘤抑制剂的口袋域对其功能至关重要,并且是人乳头瘤病毒E7瘤蛋白在宫癌中的点. 结构分析揭示了E7如何结合Rb,为癌症机制提供了洞察力.
科学领域:
- 结构生物学 结构生物学
- 分子瘤学分子瘤学
- 病毒学 病毒学
背景情况:
- 视网母细胞瘤 (Rb) 瘤抑制蛋白调节细胞循环,并且在许多癌症中被禁用.
- 人类乳头瘤病毒 (HPV) E7coprotein是宫癌发展的关键因素,主要是通过其与Rb.
- 在分子水平上了解Rb-E7相互作用对于开发向癌症疗法至关重要.
研究的目的:
- 阐明视网膜母细胞瘤 (Rb) 蛋白口袋域与人类乳头瘤病毒 (HPV) E7 基蛋白之间的相互作用的结构基础.
- 为了确定Rb-E7复合形成中所涉及的保存的结合点和结构特征.
- 探索对理解其他Rb结合蛋白及其在细胞过程中的作用的潜在影响.
主要方法:
- 使用X射线晶体学来确定与E7结合的Rb口袋域的高分辨率结构.
- 结构分析侧重于保存的图案,结合接口和与其他蛋白质结合部位的相似性.
主要成果:
- 晶体结构显示,E7中的LxCxE基因与Rb口袋域的B盒上的保存槽结合.
- Rb口袋域的A-box对于B-box的稳定折叠至关重要.
- 保存的A-B接口表明Rb口袋域上可能存在额外的蛋白质结合部位.
- 在B盒上的LxCxE结合部位与环素结合部位 (例如,环素A的Cdk2结合部位) 和转录因子结合部位 (例如,TFIIB的TBP结合部位) 具有结构上的相似性.
结论:
- 结构数据提供了详细的分子理解HPV E7如何使Rb瘤抑制剂失活.
- 这些发现突显了蛋白质-蛋白质相互作用中保存的结构特征的重要性,其中包括Rb口袋域.
- 与其他结合位点的相似性表明,Rb口袋域可能参与各种与细胞周期调节和癌症相关的蛋白相互作用网络.
相关概念视频
01:23Negative Regulator Molecules
Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
01:03Rous Sarcoma Virus (RSV) and Cancer
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:03Rous Sarcoma Virus (RSV) and Cancer
Rous Sarcoma virus or RSV was discovered by F. Peyton Rous in the year 1911 as a filterable transmissible agent that could cause tumors in chickens. He won a Nobel Prize for this discovery in 1966. His experiments clearly demonstrated that some cancers could be caused by infectious agents and led to the discovery of many more cancer-causing viruses in animals as well as humans.
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...
RSV is a retrovirus that contains two copies of a plus-strand RNA genome. Its genome consists of four main open...