The oligomerization of the coiled coil-domain of occludin is redox sensitive.

The transmembrane tight junction protein occludin is sensitive to oxidative stress. Occludin oligomerizes; however, its function in the tight junction is unknown. The cytosolic C-terminal tail contains a coiled coil-domain and forms dimers contributing to the oligomerization. The regulation of the oligomerization remains unclear. As the domain area contains sulfhydryl residues, we tested the hypothesis that the dimerization of the coiled coil-domain depends on these residues. We showed that the dimerization is modulated by the thiol concentration in the low-millimolar range, which is relevant both for physiological and pathophysiological conditions. Masking the sulfhydryl residues in the fragment by covalent binding of 4-vinyl pyridine prevented the dimerization but did not affect its helical structure and cylindric shape. The data demonstrate, for the first time, that disulfide bridge formation of murine cystein 408 is involved in the dimerization. This process is redox-sensitive but the secondary structure of the domain is not. It is concluded that the dimerization of occludin may play a regulatory role in the tight junction assembly under physiological and pathological conditions.