(757h) Association Patterns of Claudin Proteins Impact the Tight Junction Permeability

Claudin—the protein family—responsible for imparting selectivity to the tight junctions is expressed in varying proportions and combinations in the epithelial and endothelial tissues throughout the body. Despite being members of the same family, the interfaces formed by different claudins show stark variations in their selectivity and permeability. Moreover, claudins exhibit preferential behavior towards forming homomeric or heteromeric interfaces depending on the type of interacting claudin species, and in case of several diseases altered expression of one or more claudin species has been implicated in compromised tight junction barriers. For example, a normal lung epithelium expressing major proportions of claudins 3, 4 and 18 has been observed to result in reduced expression of these claudins in case of lung diseases such as alcoholic lung syndrome, coupled with an upregulation of claudin-5 with a subsequent loss of barrier function. However, claudin-5 in the blood-brain barrier tight junctions are known to increase the endothelial barrier. In this study, we performed a comparative analysis of homomeric and heteromeric cis interfaces formed by the key claudins of the lungs along with claudin-5 using rigorous computational methods. With this, we lay down a basic understanding of the structural and biochemical properties of specific protein interfaces leading to the preferential behavior of homo/heteromeric interface formation, further leading to unique selective properties of the resulting tight junctions.