همایش ملی بیوانفورماتیک ایران

صفحه اصلی / 4th international edition and 13th Iranian Conference on Bioinformatics

In Silico Analysis of the R410W Mutation in ZP1: Effects on Protein Stability and Interactions

نویسندگان :

Seyedeh Zahra Mousavi¹ Pegah Kouhi² Zeinab Rokhsattalab³ Mehdi Totonchi⁴

1- tarbiat modares university 2- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran 3- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran 4- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

کلمات کلیدی :

ZP1،R410W،point mutation،stability prediction،female infertility

چکیده :

Introduction The human zona pellucida (ZP) is an extracellular glycoprotein matrix surrounding the oocyte, playing a critical role in oocyte maturation, sperm-egg interactions during fertilization, and early embryonic protection. It comprises four glycoproteins, including ZP1, which contributes to its structural integrity and function. Mutations in ZP1 have been linked to structural and functional abnormalities of the zona pellucida, leading to female infertility associated with zona pellucida deficiency and Empty Follicle Syndrome (EFS). Among these, the R410W point mutation is associated with oocyte degeneration and the absence of a surrounding zona pellucida, underscoring its potential impact on protein stability and interaction dynamics. This study evaluates the effects of the R410W substitution on ZP1 protein stability and non-covalent interactions using bioinformatics tools. Methods The sequence of the ZP1 protein was accessed from the uniport database (P60852). The impact of the R410W variant on the stability of the ZP1 protein was assessed using MUpro, I-Mutant, and PremPS prediction tools. The findings from these tools were expressed as ΔΔG values, where a negative value indicates a destabilizing effect from a single point mutation, while a positive value in PremPS indicates a destabilizing mutation. Additionally, the PremPS tool was employed to calculate and visualize the non-covalent interactions involving residue 410 with other residues in both the native and mutant forms of the ZP1 protein. Results The ΔΔG values obtained from the three online tools uniformly indicate a reduction in the stability of the mutant protein, with values of -0.68797423 for MUpro, -0.50 for I-Mutant 2, and 0.71 for PremPS. Furthermore, the results from the PremPS database highlighted the loss of a hydrophobic bond between W410 and P537 residues, as well as some van der Waals interactions with Y420 residue and two ionic bonds with E439 residue that were present in the wildtype protein. Additionally, the mutant ZP1 protein exhibited one polar and one hydrophobic bond with E408 that were not present in the wildtype. Conclusion These findings highlight the potential implications of the R410W substitution on the structural integrity and stability properties of the ZP1 protein.