Cytokinesis is the process in which the cytoplasm is divided into two daughter cells after nuclear division in the cell division. In somatic cells, cytokinesis requires ALIX (or TSG101) and the midbody protein centrosomal protein (CEP55) to activate cell abscission. In germ cells, in contrast, CEP55 forms intercellular bridges with testis-expressed gene 14 (TEX14), by which the cell abscission is blocked. These intercellular bridges also play important roles in synchronization of germ cells, especially in spermatogenesis, by passage of organelles and molecules between germ cells. So, if TEX14 is deleted intentionally, intercellular bridges are disrupted, leading to sterility. These functions of TEX14 may provide information in the inactivation of the abscission to suppress the proliferation of cancer cells. Previous experimental studies showed that a high affinity and a low dissociation rate of TEX14 to CEP55 via the AxGPPx3YxPP (Ala793, Gly795, Pro796, Pro797, Tyr801, Pro803 and Pro804) motif of TEX14 prevents ALIX from binding and inactivates the germ cell abscission. However, the detailed information about how TEX14 interacts with CEP55 to prevent the cell abscission is still insufficient. Hence, to obtain more specific details about the interaction between CEP55 and TEX14, which is not easy to identify in experiments, we performed metadynamics simulations using atomistic models of CEP55 and TEX14. Our results show that the Tyr801 residue of TEX14 binds to CEP55 stronger than other residues of TEX14 by forming a strong hydrogen bond with Glu192 residue of CEP55, which is consistent with previous experimental studies. The binding Gibbs free energy surface calculated by the metadynamics simulation is also in good agreements with experimental data. In the future, we plan to study other peptides containing the AxGPPx3YxPP motif of TEX14 as a candidate for the suppressor of cancer cell proliferation.

Metadynamics simulation studies of the interaction between TEX14 and CEP55

254th National Meeting (2017)

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