单分子成像揭示了宿主酸对SARS-CoV-2尖端受体结合域的全刺激
Marco A Díaz-Salinas1, Aastha Jain1, Natasha D Durham1
1Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Science advances
|July 17, 2024
概括
严重急性呼吸道综合征冠状病毒2 (SARS-CoV-2) 尖端蛋白N终端域结合酸,增强病毒附着和ACE2受体结合. 这种相互作用在异质上调节尖端蛋白的构造,帮助病毒进入.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 在SARS-CoV-2尖端葡萄糖蛋白 (S) 对于病毒的入口至关重要,调解与ACE2受体的结合.
- S蛋白的N端域 (NTD) 与宿主细胞上的酸 (SA) 相互作用,但其功能意义尚不清楚.
研究的目的:
- 为了研究NTD-SA相互作用在SARS-CoV-2输入中的功能作用.
- 阐明NTD-SA结合如何影响S蛋白形状和ACE2参与.
主要方法:
- 单分子Förster共振能量转移 (smFRET) 对单个S调整器的成像.
- 对针对NTD的抗体中和机制的分析.
主要成果:
- NTD-SA相互作用显著增强了SARS-CoV-2对细胞的附着.
- 对NTD的SA结合以全质的方式促进了ACE2结合部位对S蛋白的暴露.
- 针对NTD的抗体抑制SA结合,有助于病毒中和.
结论:
- NTD-SA相互作用是S蛋白形态动态的关键调节器,促进了ACE2结合和病毒进入.
- 准NTD-SA相互作用代表了针对SARS-CoV-2的潜在治疗策略.
相关概念视频
Ligand Binding and Linkage
4.8K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked. In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.8K
GPCRs Regulate Adenylyl Cylase Activity
5.4K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.4K
Allosteric Regulation
57.8K
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
57.8K
Allosteric Proteins-ATCase
5.7K
Binding sites linkages can regulate a protein's function. For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.7K
G Protein-coupled Receptors
11.7K
G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
11.7K
Conjugated Proteins
18.3K
Simple proteins and protein complexes contain only amino acids. In contrast, many other proteins, called conjugated proteins, covalently bond with non-protein moieties.
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
Nucleoproteins are protein complexes that contain nucleic acids, categorized as deoxyribonucleoproteins (DNPs) or ribonucleoproteins (RNPs) respectively. The nucleosome is a typical example of a DNP where nuclear DNA is associated with histone proteins. The major antigen for the Covid-19 virus SARS-CoV is an RNP that is critical...
18.3K


