Morphologic determinant of tight junctions revealed by claudin-3 structures
Morphologic determinant of tight junctions revealed by claudin-3 structures
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DOI：
10.1038/s41467-019-08760-7
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发表时间：
2019-02-18
影响因子：
16.6
通讯作者：
Fujiyoshi, Yoshinori
中科院分区：
文献类型：
--
作者：
Nakamura, Shun;Irie, Katsumasa;Fujiyoshi, Yoshinori
紧密连接是一种细胞黏附装置，在上皮细胞旁间隙起屏障和/或通道的作用。Claudin是紧密连接的主要成分，它聚合形成具有不同形态的紧密连接链，这可能与它们的功能相关。在这里，我们介绍了哺乳动物claudin-3的晶体结构，分辨率为3.6埃。与其他亚型相比，claudin-3的第三个跨膜螺旋明显弯曲。对另外两个突变体进行的结构分析表明，根据残基的不同，该螺旋具有弯曲或直的结构，其中一个突变代表第三螺旋中的其他亚型。螺旋弯曲的存在或不存在会改变与claudin-claudin相互作用相关的残基的位置，并影响紧密连接链的形态和粘附性。这些结果唤起了在天然上皮中观察到的具有不同形态的紧密连接链形成的模型--直链或曲线链。
Tight junction is a cell adhesion apparatus functioning as barrier and/or channel in the paracellular spaces of epithelia. Claudin is the major component of tight junction and polymerizes to form tight junction strands with various morphologies that may correlate with their functions. Here we present the crystal structure of mammalian claudin-3 at 3.6 angstrom resolution. The third transmembrane helix of claudin-3 is clearly bent compared with that of other subtypes. Structural analysis of additional two mutants with a single mutation representing other subtypes in the third helix indicates that this helix takes a bent or straight structure depending on the residue. The presence or absence of the helix bending changes the positions of residues related to claudin-claudin interactions and affects the morphology and adhesiveness of the tight junction strands. These results evoke a model for tight junction strand formation with different morphologies - straight or curvy strands - observed in native epithelia.