ИСТИНА

Background/Objectives: We previously generated Cdh13∆Exon3 mice lacking exon 3 in the Cdh13 gene (T-cadherin) and described their phenotype. While these mice exhibited normal gross morphology, their body weight was lower than of WT mice. Upon physical training the systolic blood pressure was significantly elevated. The plasma adiponectin and the AMPK phosphorylation level in skeletal muscles and myocardium of Cdh13∆Exon3 mice were elevated. Herein, we investigated the relevance of the truncated form of murine T-cadherin in the context of human T- cadherin. Methods: To predict the protein folding, we applied the ColabFold. The best model was refined by relaxation based on the pLDDT using AMBER. Results: Comparative analysis of the truncated and full-length mouse T-cadherin revealed the presence of a prodomain in the full-length T-cadherin protein and its absence in the truncated form T-cadherin lacking the 3rd exon. The structure with the highest cumulative pLDDT score was selected. Conclusion: Further investigations are needed to elucidate the underlying mechanisms of physiological effects of truncated T-cadherin, focusing on interactions between T-cadherin and its ligands. In the untruncated form, the previously predicted pro-cadherin domain, identified by InterPro, is indeed present, contrasting with its absence in the truncated form. Positioned as the second domain in the T-cadherin structure, the pro-cadherin domain functions as part of the extracellular domain alongside the 5 cadherin domains. Meanwhile, as indicated by InterPro Phobius results, the transmembrane and intracellular domains reside at the opposite C-terminus of T-cadherin. These findings lay the groundwork for further study on assessing T-cadherin's binding activity with its ligands in docking studies. Grant References: The study was supported by the Russian Science Foundation, grant No. 23-11-00205, under the State Assignment # 03р-23/110- 03 of Lomonosov MSU.