Molecular architecture and assembly of the tight junction backbone

Biochim Biophys Acta Biomembr. 2020 Jul 1;1862(7):183279. doi: 10.1016/j.bbamem.2020.183279. Epub 2020 Mar 26.


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.

Keywords: Barrier and channel function; Claudin; Joined double-row model; Molecular structure; Tight junction; Tight junction strand assembly.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Claudins / chemistry*
  • Claudins / genetics
  • Computer Simulation
  • HEK293 Cells
  • Humans
  • Microscopy, Electron
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Mutagenesis
  • Protein Conformation*
  • Protein Multimerization
  • Tight Junctions / chemistry*
  • Tight Junctions / genetics*
  • Tight Junctions / ultrastructure


  • Claudins
  • claudin 15