约束FimH捕捞绑定机制的绑定场地可塑性规则
Olivier Languin-Cattoën1, Fabio Sterpone1, Guillaume Stirnemann1
1CNRS Laboratoire de Biochimie Théorique, Institut de Biologie Physico-Chimique, Université Paris Cité, PSL University, Paris, France.
Biophysical journal
|June 2, 2023
概括
细菌粘合物FimH使用捕获键机制在尿路感染期间粘附于宿主细胞. 新的研究表明,强力直接有利于高亲和度的结合状态,解释了它的强烈依恋.
科学领域:
- 微生物学和分子生物学
- 生物物理学的生物物理.
- 结构生物学 结构生物学
背景情况:
- 细菌的fimbrial粘合物FimH,在大肠杆菌1型 pili上发现,介导结合人体上皮质,对于尿路感染至关重要.
- FimH表现出捕捉键行为,在施加力下加强其相互作用,帮助细菌抵抗尿液流动.
- 目前的模型提出强力诱导的全变化,分离域以增加结合亲和力,但晶体结构显示类似的结合点.
研究的目的:
- 调查FimH的捕获结合机制的分子起源以及结构和亲和数据之间的差异.
- 探索结合点形状和力量在FimH-糖甘相互作用中的作用.
主要方法:
- 分子动力学模拟与增强采样技术相结合.
- 对结合部位构造及其在不同全性状态下的群体的分析.
- 对强力对结合点形状的直接影响的研究.
主要成果:
- 鉴定出不同的结合点形状,这些形状在静态晶体结构中并不明显,显著影响了表面亲和力.
- 在两种全性状态之间展示了这些构造的独特种群,与实验亲和度测量相关.
- 揭示了应用力直接有利于高亲和度结合点构造,除了域区分外.
结论:
- FimH的捕获结合机制涉及受力影响的结合点构造的动态相互作用.
- 一个"本地"的捕获结合效应,在这种效应中,强力直接稳定了高亲和度状态,补充了已知的"全球"全osteric调节.
- 这些发现为FimH介导的粘附和细菌持久性提供了更全面的分子理解.
相关概念视频
00:49Ligand 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
01:49Conserved Binding Sites
4.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.2K
01:19Allosteric Proteins-ATCase
5.8K
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...
5.8K
02:40Ligand Binding Sites
12.9K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
12.9K
01:58Cooperative Allosteric Transitions
7.9K
Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
7.9K
02:53Conservative Site-specific Recombination and Phase Variation
6.0K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.0K