相关实验视频

Updated: May 15, 2025

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission

Published on: August 16, 2018

生理学Ashwell-Morell受体连接体的组成和拓学决定因素

John Hintze^1,2, Robert Fraumeni¹, Noortje de Haan^2,3

¹Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA 92037.

Proceedings of the National Academy of Sciences of the United States of America

|April 10, 2025

概括

阿什韦尔-莫雷尔受体 (AMR) 将特定的N-甘氨酸与血糖蛋白结合起来. 这项研究表明,AMR不结合化N-甘氨酸,但二元化可能会从双结构中产生连接体.

科学领域:

生物化学生物化学
细胞生物学细胞生物学
葡萄糖科学 (Glycoscience) 是一种科学.

背景情况:

阿什韦尔-莫雷尔受体 (AMR) 是一种关键的哺乳动物莱克,参与糖蛋白清除和宿主防御.
了解AMR配体的决定因素至关重要,但之前关于N-甘氨酸结合的发现是矛盾的.
大多数循环中的葡萄糖蛋白都含有双年性N-葡萄糖,以前认为这些葡萄糖不是AMR配体.

研究的目的:

研究Ashwell-Morell受体 (AMR) 连接体结合的组成和拓要求.
澄清N-glycan化和分支在AMR识别中的作用.
为了确定糖蛋白的二元化是否可以产生AMR连接体.

主要方法:

制造的糖基工程肠道性酸酶 (IAP) 含有定义的双年,三年和四年N-glycans.
经过修改的IAP糖形与α2-6或α2-3酸链接.
评估了同质IAP糖形和二聚体的AMR结合和清除.

主要成果:

当N-甘氨酸主要被化以α2-6或α2-3链接时,AMR没有显著地与IAP结合.
在IAP单体上没有观察到AMR结合的双年期N-甘氨酸.
IAP单体的二元化导致了两年内N-甘氨酸的近似,可能形成多价值的脱氧化联体.

结论:

酸链接 (α2-6和α2-3) 在N-甘氨酸上抑制阿什韦尔-莫雷尔受体 (AMR) 结合.
仅仅两年制的N-甘氨酸对抗药物耐药性的识别是不够的.
糖蛋白二元化可以创建多价值的脱氧化结构,可以作为生理AMR连接体.

关键词:

阿什韦尔莫雷尔受体的受体血液中的蛋白质稳定.葡萄糖酶化是什么? 葡萄糖酶化是什么?莱克连接剂莱克连接剂莱克受体的受体是什么

更多相关视频

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Author Spotlight: Exploring Cellular Processes by Modeling Ligands in Cryo-EM Maps

Published on: July 19, 2024

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET

Visualizing the Conformational Dynamics of Membrane Receptors Using Single-Molecule FRET

Published on: August 17, 2022

相关概念视频

The Two-State Receptor Model

The Two-State Receptor Model

The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...

Ligand Binding Sites

Ligand Binding Sites

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...

Ligand Binding and Linkage

Ligand Binding and Linkage

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...

Drug-Receptor Interactions

Drug-Receptor Interactions

Drug-receptor interaction describes the binding of receptors by drugs, but not all drug-receptor interactions result in activation and tissue response. For instance, the binding of agonists activates the receptor to generate a cellular reaction, while antagonists bind to receptors without causing their activation.
Several parameters, such as the drug's affinity for its receptor and its efficacy, which is its ability to activate the receptor, determine the drug's effect on the tissue....

Adrenergic Agonists: Chemistry and Structure-Activity Relationship

Adrenergic Agonists: Chemistry and Structure-Activity Relationship

Adrenergic agonists' structure-activity relationship (SAR) determines their selectivity and efficacy. These agonists comprise a phenylethylamine moiety with an aromatic ring and an ethylamine side chain.
Aromatic ring substitutions: Substituting the aromatic ring with –OH groups at positions 3 and 4 yields catecholamines (e.g., epinephrine), which have a high affinity for adrenoceptors. Hydrogen bonding between –OH groups and receptors enhances adrenergic activity.
Separation of...

Internal Receptors

Internal Receptors

Many cellular signals are hydrophilic and therefore cannot pass through the plasma membrane. However, small or hydrophobic signaling molecules can cross the hydrophobic core of the plasma membrane and bind to internal, or intracellular, receptors that reside within the cell. Many mammalian steroid hormones use this mechanism of cell signaling, as does nitric oxide (NO) gas.