Narayanaswamy Radhakrishnan, Harika Vemugadda, Prabhakaran Vasantha-Srinivasan
Department of Biochemistry, Saveetha Medical College and Hospital, Saveetha Institute of Medical and Technical Sciences (Deemed to be University), Chennai, IND.
Department of Bioinformatics, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences (Deemed to be University), Chennai, IND.
Cureus. 2024 Aug 6;16(8):e66332. doi: 10.7759/cureus.66332. eCollection 2024 Aug.
Background Human nephrin (hNeph) (podocyte protein) has been known to be involved in both the formation and maintenance of the slit diaphragm (SD) and also acts as a hub protein in the podocyte by modulating cell polarity, cell survival, cell adhesion, cytoskeletal organization, mechano-sensing, and SD turn-over. Methodology In the present investigation, we aimed to analyse the hNeph and mouse nephrin (mNeph) and their interactions with 13 proteins using the molecular docking method. The 13 selected human proteins which include matrix metalloproteinases (MMP 2 and 9), retinol-binding proteins (RBP 3 and 4), kallikrein 1 (KLK 1), uromodulin, insulin-like growth factor binding protein 7 (IGFBP7), cystatin C, podocin, beta arrestin 1, vang-like protein 2 (VANGL2), dynamin 1, and tensin-like C1 domain-containing phosphatase (TENC1) were studied on the docking analysis of hNeph and mNeph by using the HDOCK (protein-protein) docking method. In addition, the physicochemical (PC) properties of 15 proteins were performed using the ProtParam web server. Results In the present investigation, five chosen human proteins, namely, IGFBP7, cystatin C, podocin, VANGL2, and TENC1, have exhibited theoretical isoelectric point (PI) values greater than 7.0. The protein-protein docking analysis has shown that hKLK and hVANGL2 exhibited the maximum docking score of -206.39 kcal/mol and -329.28 (kcal/mol) with the target proteins mNeph and hNeph, respectively. Conclusions Thus, the current finding highlights the interactions of hNeph and mNeph with 13 chosen proteins, which may help in renal disease management.
背景 已知人源nephrin（hNeph，足细胞蛋白）参与裂孔隔膜（SD）的形成与维持，并且通过调节细胞极性、细胞存活、细胞黏附、细胞骨架组织、机械传感以及SD更新，在足细胞中充当枢纽蛋白。方法 在本研究中，我们旨在使用分子对接方法分析hNeph和小鼠nephrin（mNeph）及其与13种蛋白质的相互作用。所选择的13种人类蛋白质包括基质金属蛋白酶（MMP 2和9）、视黄醇结合蛋白（RBP 3和4）、激肽释放酶1（KLK 1）、尿调节蛋白、胰岛素样生长因子结合蛋白7（IGFBP7）、胱抑素C、足突融合蛋白、β抑制蛋白1、类vang蛋白2（VANGL2）、发动蛋白1以及含张力蛋白样C1结构域的磷酸酶（TENC1），通过使用HDOCK（蛋白质-蛋白质）对接方法对hNeph和mNeph进行对接分析研究。此外，使用ProtParam网络服务器对15种蛋白质的物理化学（PC）性质进行了分析。结果 在本研究中，所选择的5种人类蛋白质，即IGFBP7,、胱抑素C、足突融合蛋白、VANGL2和TENC1，表现出理论等电点（PI）值大于7.0。蛋白质-蛋白质对接分析表明，hKLK和hVANGL2与目标蛋白mNeph和hNeph的对接分数最高，分别为-206.39千卡/摩尔和-329.28（千卡/摩尔）。结论 因此，当前研究结果突出了hNeph和mNeph与13种所选蛋白质的相互作用，这可能有助于肾脏疾病的管理。
