全球艾滋病毒-人类蛋白质复合体的风景
Stefanie Jäger1, Peter Cimermancic, Natali Gulbahce
1Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94158, USA.
Nature
|December 23, 2011
概括
研究人员绘制了人类免疫缺陷病毒 (HIV) 蛋白与宿主细胞的相互作用. 这项研究确定了497种HIV - 人类蛋白相互作用,揭示了保存的宿主标和潜在的复制抑制剂.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 人类免疫缺陷病毒 (HIV) 由于其有限的基因组而依赖宿主细胞机械进行复制.
- 了解宿主-病原体相互作用是解读病毒复制策略和开发干预措施的关键.
研究的目的:
- 系统地确定所有18种HIV-1蛋白和宿主蛋白之间的物理相互作用.
- 为了全面地绘制感染期间艾滋病毒对宿主细胞机械的重新连接.
主要方法:
- 使用亲和标记和净化质谱法捕获HIV宿主蛋白质复合体.
- 开发了一种定量评分系统,即MiST,用于识别高可信度相互作用.
- 为了更广泛的应用,在两个不同的人类细胞系 (HEK293和Jurkat) 上进行了实验.
主要成果:
- 确定了497个高可信度的HIV-人类蛋白质-蛋白质相互作用,涉及435种独特的人类蛋白质.
- 大约40%的这些相互作用在两种测试的细胞类型中都保留了.
- 已识别的与HIV相互作用的宿主蛋白,特别是那些在灵长类动物中保存的蛋白,经常参与抑制病毒复制.
结论:
- 该研究提供了艾滋病毒与宿主蛋白相互作用的详细地图,这对于理解细胞过程的病毒操纵至关重要.
- 发现抑制HIV复制的宿主蛋白质为新的治疗策略提供了潜在的目标.
- 被劫持的宿主蛋白质的保存性表明了进化压力和病毒生命周期中的潜在漏洞.
相关概念视频
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
01:57Protein Complexes with Interchangeable Parts
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order to...
02:41Protein Complex Assembly
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
02:41Protein Complex Assembly
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
02:04Protein-protein Interfaces
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...
02:04Protein-Protein Interfaces
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...