Abstract 1907 Noncovalent Interactions in the Dimerization of Mucin 16 Transmembrane Domain

Mucins are proteins that contribute to the mucus barrier that protects epithelial cells, the cells that line the inner and outer surfaces of the body. The overexpression of mucins correlates with carcinogenesis, making mucin research an important target for further studies regarding treatments, therapies, and diagnosis techniques. Mucin 16 (MUC16) is an example of a transmembrane mucin that is specifically associated with ovarian and pancreatic cancer. Dimerization of MUC16 results in localization to the nucleus, suggesting a potential role in gene regulation. MUC16 contains two cysteine residues near its transmembrane domain (TMD) that could contribute to dimer formation due to disulfide bond formation. However, studies in our lab with the TMD of MUC16 have shown that the cysteine residues do not play a large role in dimerization. Therefore, there may be noncovalent interactions that contribute significantly to the dimerization of MUC16. Based on the amino acid sequence of the MUC16 TMD, the SmXXXSm motif may contribute to dimer formation. In previous studies, this sequence of three amino acids flanked by two small amino acids has been shown to be important in other TMD dimers in which the sequence appears. The role of this motif in MUC16 is tested using the ToxR activity assay. The assay uses beta-galactosidase as a reporter of TMD dimerization and has been used extensively to gain insights into the dimer interface between two transmembrane domains.