Leucine Zipper Motif Drives the Transmembrane Domain Dimerization of E-cadherin
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E-cadherin is a transmembrane glycoprotein which is involved in the Ca2+-dependent cell–cell adhesion, and the adhesiveness is heavily dependent on the homodimerization of this molecule. Previous studies have shown that both the extracellular domain and cytoplasmic domain of E-cadherin contribute to its homodimerization. However, the roles of the transmembrane(TM) domain in the E-cadherin homodimerization have not been discussed in detail. In our experiments, SDS-PAGE showed higher molecular weight bands for the synthetic E-cadherin TM peptide, which indicated that the E-cadherin TM peptide is able to dimerize in the SDS micelle. The TOXCAT assay proved that the E-cadherin TM domain can form a moderate homo-oligomer in the Escherichia coli inner membrane. Furthermore, mutational analyses using the TOXCAT assays revealed that, instead of the common GxxxG dimerization motif, the leucine zipper motif is essential for the dimerization of the E-cadherin TM domain. Combining our experiment data and the computational simulation results, we provide insights for understanding the roles of the TM domain in the E-cadherin dimerization.
KeywordsDimerization E-cadherin GxxxG motif Leucine zipper motif TOXCAT Transmembrane domain
This work was supported by the National Basic Research Program of China (973 program) (2013CB910700) and the National Natural Science Foundation of China (No. 20932003, No. 21002007), and Beijing NOVA Programme (xx2013010).
Conflict of interest
We declare that we have no conflict of interest. No patients and animals are involved.
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