在UNC5C中识别ZU5域作为希桑德林A的潜在受体:实验和计算见解
Jiaxin Zhang1, Zhuanhong Wang2, Jurong Zeng1
1Shaanxi Key Laboratory of Brain Disorders & Institute of Basic and Translational Medicine, Department of Basic Medicine, Xi'an Medical University, Xi'an 710021, China.
Bioorganic chemistry
|February 22, 2026
概括
斯基桑德林A与UNC5C的ZU5域结合,通过广泛的查来确定. 这种由和特异力驱动的相互作用遵循诱导适应原理,有助于神经退行性疾病研究.
科学领域:
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 斯基桑德林A具有已知的临床潜力,但其体内标需要全面识别.
- 了解希桑德林A的分子相互作用对于阐明其药理机制至关重要.
研究的目的:
- 选潜在的 in vivo 接收器的斯基桑德林A.A. 的选.
- 调查斯基桑德林A与网氨酸受体UNC5C异型X1 (ZU5) 的ZU5域之间的详细结合机制.
主要方法:
- 体显示图书馆查和基本局部对齐搜索工具 (BLAST) 用于受体识别.
- 光光谱学,异热定位热量测量 (ITC) 和分子动力学 (MD) 模拟用于结合分析.
主要成果:
- 选了39个潜在的schisandrin A体内受体,ZU5被确定为候选者.
- 斯基桑德林A与ZU5同等结合,由力,范德瓦尔斯力和键驱动,与诱导适合理论相一致.
- 特定的氨基酸残留物 (Leu61, Leu96) 和斯基桑德林A的结构特征 (双环,甲氧基) 是结合的关键.
结论:
- 这项研究确定了ZU5作为一个schisandrin A受体,并阐明了结合机制.
- 这些发现为神经退行性疾病机制研究和基于结构的药物设计提供了宝贵的见解,用于Schisandrin A.
更多相关视频
16:16Genetically-encoded Molecular Probes to Study G Protein-coupled Receptors
Published on: September 13, 2013
15.8K
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
9.1K
相关概念视频
G Protein-coupled Receptors
18.1K
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...
18.1K
Pinching-off of Coated Vesicles
4.3K
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
4.3K
Assembly of Signaling Complexes
6.7K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.7K
Conservation of Protein Domains Over Different Proteins
14.8K
Protein domains are small structurally independent units that are part of a single amino acid chain. Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
14.8K
