Crystal Structure of a Claudin Provides Insight into the Architecture of Tight Junctions

• DOI: 10.1126/science.1248571
• Publication Date: 2014-04-17T18:44:35Z
• Authors: Hiroshi Suzuki; Tomohiro Nishizawa; Kazutoshi Tani; Yuji Yamazaki; Atsushi Tamura; Ryuichiro Ishitani; Naoshi Dohmae; Sachiko Tsukita; Osamu Nureki; Yoshinori Fujiyoshi
• Keywords: Models, Molecular; 0301 basic medicine; Protein Folding; Protein Conformation; Amino Acid Motifs; Molecular Sequence Data; Static Electricity; Crystallography, X-Ray; Protein Structure, Secondary; Protein Structure, Tertiary; Tight Junctions; Mice; Protein Subunits; 03 medical and health sciences; Claudins; Animals; Amino Acid Sequence

How Tight?

In metazoans, sheets of epithelial cells separate different tissue spaces and control their composition. Tight junctions are cell-cell adhesion structures in these cell sheets that form a seal between cells but also provide some selective permeability to ions and small molecules. Claudins are the main constituents of tight junctions, and mutations in claudins cause inherited human disorders involving the disruption of ionic balance.

Suzuki et al.

(p. 304 ) report the structure of mouse claudin-15 at 2.4 angstrom resolution, which shows an extracellular β-sheet domain anchored to a transmembrane four-helix bundle. The electrostatic distribution on the claudin surface reveals a negatively charged groove in the extracellular domain that may provide a pathway for positive ions.