概括
李斯特菌粘附蛋白 (LAP) 和Hsp60形成一个复合物,增强肠道药物吸收. 这一发现提供了一种新的策略,可以在没有不良影响的情况下口服生物药物.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 李斯特菌的粘附蛋白 (LAP) 通过与Hsp60相互作用来调节紧密结 (TJs),帮助李斯特菌单细胞原体的转移.
- 现有的TJ调制器 (TJM) 已经显示出可变和限制性效应.
研究的目的:
- 在结构上描述LAP-Hsp60复合体.
- 评估纯化的LAP作为一种TJM,用于增强口服药物输送.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 和计算分析,单独确定LAP的结构以及与Hsp60.0复合的结构.
- 用小鼠模型来评估LAP介导的药物吸收.
主要成果:
- LAP结构揭示了多重体互锁的二分体和四分体,其中N域与Hsp60相互作用,C域结合InlB.
- 拉皮促进了范科米辛和德斯莫普林素通过肠道屏障的吸收,而不会引起炎症或TJ损伤.
结论:
- 在结构上,LAP-Hsp60复合体是定义的,并作为一个有效的TJM.
- 拉普及其模仿剂对改善口服生物药物输送具有前景.
更多相关视频
06:43Functional Assessment of Intestinal Tight Junction Barrier and Ion Permeability in Native Tissue by Ussing Chamber Technique
Published on: May 26, 2021
5.4K
10:31Detection of In Situ Protein-protein Complexes at the Drosophila Larval Neuromuscular Junction Using Proximity Ligation Assay
Published on: January 20, 2015
13.1K
相关概念视频
Tight Junctions
5.2K
Tight junctions are molecular seals between cells that prevent the leaking of fluids, ions, and other small solutes across cavities and compartments in multicellular organisms. They are mainly composed of claudin and occludin transmembrane proteins, and other proteins such as tricellulin and JAM (junctional adhesion molecule). All these proteins are 4-pass transmembrane proteins, except JAM, which is a single-pass transmembrane protein belonging to the immunoglobulin superfamily. The...
5.2K
Anchoring Junctions
3.7K
Anchoring junctions are multiprotein complexes that help cells connect to other cells and the extracellular matrix. Anchoring junctions are present on the lateral and basal surfaces of cells, providing strong and flexible connections. Focal adhesions are often formed due to cell interactions with the ECM substrata, which initiate signal transduction via kinase cascades and other mechanisms. Together, they provide stability and tissue integrity. There are three types of anchoring junctions:...
3.7K
Adherens Junctions
4.7K
Strong contact points between adjacent cells anchor them to each other, forming tissues. Such anchoring junctions are of two types – adherens junctions and desmosomes. Adherens junctions are abundant in tissues such as epithelium and endothelium, forming a continuous zone of adhesion called the adhesion belt. In other tissues, such as heart muscle, they appear as clusters, linking the cells to produce coordinated heart muscle contraction.
Adherens Junctions are Dynamic
Adherens Junctions are Dynamic
4.7K
Tension Response at Adherens Junctions
2.6K
The adherens junctions that anchor cells together are multi-protein complexes that dynamically adapt to mechanical stimuli such as tensile forces and shear stress. Mechanosensory proteins in these junctions can sense such mechanical stimuli and undergo a shift in their conformation, resulting in an altered function — a process called mechanotransduction.
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
α-Catenin as a Mechanosensory Protein
The α-catenin of adherens junctions is an allosteric protein with three VH (vinculin...
2.6K
Hedgehog Signaling Pathway
7.3K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.3K
Cell-matrix's Response to Mechanical Forces
2.6K
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
2.6K
