人类ARF6-GTP激活霍乱毒素的结构基础
Claire J O'Neal1, Michael G Jobling, Randall K Holmes
1Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
概括
霍乱毒素利用人类的ADP-ribosylation因子 (ARF) 引起疾病. 结构研究揭示了ARF结合如何改变毒素,使其能够激活关键信号蛋白并引起腹.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 微生物学 微生物学
背景情况:
- 霍乱病毒 (Vibrio cholerae) 引起霍乱,一种严重的腹疾病.
- 霍乱毒素A1亚单元 (CTA1) 催化了人类信号蛋白质GSalpha的ADP-ribosylation.
- 这一过程对于霍乱病原发生是必不可少的.
研究的目的:
- 阐明人类ADP-ribosylation因子 (ARFs) 激活霍乱毒素的结构机制.
- 了解ARF结合如何诱导CTA1中的构造变化以获得基质.
主要方法:
- 一个CTA1:ARF6-GTP复合体的X射线晶体学.
- 分析蛋白质-蛋白质相互作用和形状变化.
主要成果:
- 在ARF6-GTP结合后,晶体结构揭示了CTA1中的戏剧性循环重排.
- 这些变化为尼古丁胺胺氨基二核酸 (NAD+) 创建了一个结合点.
- 毒素-ARF接口模仿了自然的ARF蛋白相互作用,表明分子利用.
结论:
- 霍乱毒素已经进化到劫持宿主细胞的ARF蛋白质.
- 了解这种相互作用可以了解毒素机制和潜在的治疗点.
更多相关视频
14:02Optimizing the Genetic Incorporation of Chemical Probes into GPCRs for Photo-crosslinking Mapping and Bioorthogonal Chemistry in Live Mammalian Cells
Published on: April 9, 2018
15:05Deciphering the Structural Effects of Activating EGFR Somatic Mutations with Molecular Dynamics Simulation
Published on: May 20, 2020
相关概念视频
Globular and Fibrous Proteins
Many proteins can be classified into two distinct subtypes - globular or fibrous. These two types differ in their shapes and solubilities.
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Globular proteins are also known as spheroproteins and typically are approximately round in shape. They contain a mix of amino acid types and contain differing sequences in their primary structures. Globular proteins have many different functions, such as enzymes, cellular messengers, and molecular transporters. These roles often require the proteins to be...
Generation of Straight or Branched Actin Filaments
The straight or branched structure formation of actin filaments is controlled by nucleating proteins such as the formins and Arp2/3 complex. Formin-mediated assembly results in straight filaments, whereas Arp2/3 protein complex-mediated assembly results in branched actin filaments.
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
Arp2/3 Complex
Arp2/3 complex is a seven-subunit complex consisting of two proteins similar to actin- Arp2 and Arp3, and five other subunits that help keep Arp2 and Arp3 inactive. When required, the complex is...
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...
Nucleic Acid Structure
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...
DNA Structure
DNA has a double-helix structure. The...
