Alberta RNA Research and Training Institute, Department of Chemistry and Biochemistry, University of Lethbridge, 4401 University Drive, Lethbridge, AB T1K 3M4, Canada.
Department of Microbiology, Immunology and Infectious Disease, Cumming School of Medicine, University of Calgary, 3330 Hospital Drive, Calgary, AB T2N 4N1, Canada.
Int J Mol Sci. 2021 Mar 5;22(5):2647. doi: 10.3390/ijms22052647.
Members of the human Zyxin family are LIM domain-containing proteins that perform critical cellular functions and are indispensable for cellular integrity. Despite their importance, not much is known about their structure, functions, interactions and dynamics. To provide insights into these, we used a set of in-silico tools and databases and analyzed their amino acid sequence, phylogeny, post-translational modifications, structure-dynamics, molecular interactions, and functions. Our analysis revealed that zyxin members are ohnologs. Presence of a conserved nuclear export signal composed of LxxLxL/LxxxLxL consensus sequence, as well as a possible nuclear localization signal, suggesting that Zyxin family members may have nuclear and cytoplasmic roles. The molecular modeling and structural analysis indicated that Zyxin family LIM domains share similarities with transcriptional regulators and have positively charged electrostatic patches, which may indicate that they have previously unanticipated nucleic acid binding properties. Intrinsic dynamics analysis of Lim domains suggest that only Lim1 has similar internal dynamics properties, unlike Lim2/3. Furthermore, we analyzed protein expression and mutational frequency in various malignancies, as well as mapped protein-protein interaction networks they are involved in. Overall, our comprehensive bioinformatic analysis suggests that these proteins may play important roles in mediating protein-protein and protein-nucleic acid interactions.
人类 Zyxin 家族成员是 LIM 结构域蛋白，它们具有关键的细胞功能，对细胞完整性是不可或缺的。尽管它们很重要，但人们对它们的结构、功能、相互作用和动力学知之甚少。为了深入了解这些，我们使用了一组计算机工具和数据库，分析了它们的氨基酸序列、系统发育、翻译后修饰、结构动力学、分子相互作用和功能。我们的分析表明 Zyxin 家族成员是同源物。存在由 LxxLxL/LxxxLxL 保守序列组成的核输出信号以及可能的核定位信号，表明 Zyxin 家族成员可能具有核和细胞质功能。分子建模和结构分析表明，Zyxin 家族的 LIM 结构域与转录调节剂具有相似性，并且具有带正电荷的静电斑，这可能表明它们具有以前未预料到的核酸结合特性。Lim 结构域的固有动力学分析表明，只有 Lim1 具有类似的内部动力学特性，而 Lim2/3 则不同。此外，我们还分析了它们在各种恶性肿瘤中的蛋白表达和突变频率，并绘制了它们参与的蛋白-蛋白相互作用网络。总的来说，我们的综合生物信息学分析表明，这些蛋白可能在介导蛋白-蛋白和蛋白-核酸相互作用方面发挥重要作用。
