甘酸结合蛋白如何实现GTP到GMP的组装刺激的过程性裂变?
Agnidipta Ghosh1, Gerrit J K Praefcke, Louis Renault
1Abteilung Strukturelle Biologie, Max-Planck-Institut für Molekulare Physiologie, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
Nature
|March 3, 2006
概括
人体酸结合蛋白1 (hGBP1) 使用其G域将GTP化为GMP. 这一过程涉及核酸依赖的同质化和特定的结构变化,以实现高效的催化.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 干扰素是细胞因子,在免疫系统中起着关键作用.
- 人体酸结合蛋白1 (hGBP1) 是一种干扰素--诱导蛋白.
- hGBP1是一种具有独特酶特性的GTP结合蛋白.
研究的目的:
- 为了研究hGBP1.1.的孤立的N端G域的酶性质.
- 通过hGBP1.1.阐明通过hGBP1.1.进行GTP水解的基础分子机制.
- 了解hGBP1.1中的核酸依赖性同质化和催化.
主要方法:
- 生物化学试验研究GTP水解.
- 用X射线晶体学来确定结构中间体.
- 分析蛋白质结构和生物化学数据.
主要成果:
- 孤立的hGBP1的N-终端G域保留了全部的酶活性,包括直接的GDP裂变.
- 晶体结构揭示了核酸依赖性同质化过程的分子基础.
- 通过开关区域变化调节的同质化,通过素指形成一个活跃的催化部位.
- 核酸的形状变化将基质定位为第二个水解步骤.
结论:
- hGBP1的N端G域足以实现其关键的酶功能.
- 结构洞察力解释了GTP水解和同质化机制.
- hGBP1独特的催化机制为GTP结合蛋白的功能提供了一个模型.
相关概念视频
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
Mechanical Protein Functions
Proteins perform many mechanical functions in a cell. These proteins can be classified into two general categories- proteins that generate mechanical forces and proteins that are subjected to mechanical forces. Proteins providing mechanical support to the structure of the cell, such as keratin, are subjected to mechanical force, whereas proteins involved in cell movement and transport of molecules across cell membranes, such as an ion pump, are examples of generating mechanical force.
Coat Assembly and GTPases
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
GTPases and their Regulation
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins, also known...
Large G-proteins, also known...
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
Bacterial Protein Maturation
Bacterial protein maturation is a tightly regulated process that ensures newly synthesized polypeptides achieve correct functional conformations. This maturation involves a series of modifications, folding events, and quality control steps, often assisted by specialized chaperone proteins.N-Terminal ModificationsThe maturation of bacterial polypeptides begins cotranslationally as the polypeptide exits the ribosome. The first amino acid, N-formylmethionine (fMet), is typically modified at the...


