当前位置: X-MOL 学术BBA Biomembr. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Molecular architecture and assembly of the tight junction backbone.
Biochimica et Biophysica Acta (BBA) - Biomembranes ( IF 3.4 ) Pub Date : 2020-03-26 , DOI: 10.1016/j.bbamem.2020.183279
Jörg Piontek 1 , Susanne M Krug 1 , Jonas Protze 2 , Gerd Krause 2 , Michael Fromm 1
Affiliation  

The functional and structural concept of tight junctions has developed after discovery of claudin and TAMP proteins. Many of these proteins contribute to epi- and endothelial barrier but some, in contrast, form paracellular channels. Claudins form the backbone of tight junction (TJ) strands whereas other proteins regulate TJ dynamics. The current joined double-row model of TJ strands and channels is crucially based on the linear alignment of claudin-15 in the crystal. Molecular dynamics simulations, protein docking, mutagenesis, cellular TJ reconstitution, and electron microscopy studies largely support stability and functionality of the model. Here, we summarize in silico and in vitro data about TJ strand assembly including comparison of claudin crystal structures and alternative models. Sequence comparisons, experimental and structural data substantiate differentiation of classic and non-classic claudins differing in motifs related to strand assembly. Classic claudins seem to share a similar mechanism of strand formation. Interface variations likely contribute to TJ strand flexibility. Combined in vitro/in silico studies are expected to elucidate mechanistic keys determining TJ regulation.

中文翻译:

紧密连接骨架的分子结构和组装。

在发现claudin和TAMP蛋白后,紧密连接的功能和结构概念得到发展。这些蛋白质中的许多有助于上皮和内皮屏障,但相反,一些形成旁细胞通道。claudins形成紧密连接(TJ)链的骨干,而其他蛋白质则调节TJ动力学。TJ链和通道的当前加入的双行模型至关重要地基于晶体中claudin-15的线性排列。分子动力学模拟,蛋白质对接,诱变,细胞TJ重建和电子显微镜研究在很大程度上支持了模型的稳定性和功能性。在这里,我们总结了有关TJ链组装的计算机和体外数据,包括claudin晶体结构和替代模型的比较。序列比较 实验和结构数据证实了经典和非经典claudins在与链装配相关的基序方面不同的区别。经典的claudins似乎具有相似的链形成机制。界面变化可能有助于TJ链的柔韧性。结合体外/计算机模拟研究有望阐明确定TJ调节的机制关键。
更新日期:2020-03-27
down
wechat
bug