Department of Biochemistry, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi, 110062, India.
Department of Agricultural Microbiology, Faculty of Agricultural Sciences, Aligarh Muslim University, Aligarh, UP, 202002, India.
Sci Rep. 2023 Sep 14;13(1):15262. doi: 10.1038/s41598-023-40913-z.
Sorcin (Sri), a member of penta EF-hand protein family plays a diverse role in maintaining calcium homeostasis, cell cycle and vesicular trafficking. Sri is highly conserved amongst mammals and consists of N-terminal glycine rich domain and C-terminal calcium binding domain that mediates its dimerization and interacts with different compounds. In the present study, with the help of combination of computational and molecular biology techniques, we have identified a novel isoform (Sri-N) in mouse which differs only in the C-terminal domain with that of Sri reported earlier. The novel isoform contains a new last exon that is different from the one present in the reported transcript (Sri). The presence of the novel isoform was further validated in different tissues by RT-PCR and DNA sequencing. The transcript was conceptually translated and subjected to in-silico analysis using different bioinformatics tools. The novel transcript variant encodes for a longer protein isoform without any change in the sub-cellular localization as predicted by PSORT-II online tool. Molecular modelling was performed to compare the structural changes in Sri-N and Sri isoforms. The structural characterization of the novel isoform using MD simulation depicted its overall stability under the physiological conditions. The molecular docking of proteins with various chemotherapeutic drugs revealed that their binding affinity is more for Sri-N as compared to that for the previously reported transcript Sri.
Sorcin (Sri)，五钙结合蛋白家族的一员，在维持钙稳态、细胞周期和囊泡运输中发挥着多样化的作用。Sri 在哺乳动物中高度保守，由富含甘氨酸的 N 端结构域和 C 端钙结合结构域组成，介导其二聚化并与不同的化合物相互作用。在本研究中，我们结合计算和分子生物学技术，在小鼠中鉴定出一种新型的异构体（Sri-N），它仅在 C 端结构域与先前报道的 Sri 不同。新型异构体包含一个新的最后外显子，与报告的转录本（Sri）中的外显子不同。通过 RT-PCR 和 DNA 测序在不同组织中进一步验证了新型异构体的存在。对该转录本进行了概念性翻译，并使用不同的生物信息学工具进行了计算机分析。新型转录变体编码的蛋白异构体更长，但亚细胞定位与 PSORT-II 在线工具预测的没有变化。进行了分子建模以比较 Sri-N 和 Sri 异构体的结构变化。使用 MD 模拟对新型异构体进行结构表征，描绘了其在生理条件下的整体稳定性。与各种化疗药物的蛋白质对接表明，与先前报道的 Sri 转录本相比，它们对 Sri-N 的结合亲和力更高。
