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International Journal of Fertility and Sterility، جلد ۸، شماره ۲.۵، صفحات ۴۷-۴۷
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عنوان انگلیسی P-30: The Effect of The T26248G Polymorphism on Putative MethyltransferaseNsun7 Protein Function and Its Role in Male Infertility
چکیده انگلیسی مقاله Background: Male infertility has many causes, including genetic infertility. The NOP2/Sun domain family, member7 (Nsun7) gene, which encodes putative methyltransferase Nsun7, has a role in sperm motility. The aim of the present study was to investigate the effect of the T26248G polymorphism on Nsun7 protein function and its role in male infertility. Materials and Methods: Semen samples were collected from the IVF centre and exon7 was amplified using forward and reverse primers. Bands on samples from oligoasthenospermic men that exhibited different patterns of movement on single-strand conformation polymorphism (SSCP) gels compared with normal samples were identified and subjected to sequencing. Results were investigated with informatics tools. Results: Direct sequencing of PCR products, along with their analysis, confirmed T26248G-transversion mutation in oligoasthenospermic men. Comparison of normal and mutant protein structures of Nsun7 indicated that the amino acid serine was converted to alanine, the structure of the helix, coil and strand was changed, and the protein folding and ligand binding sites were changed, indicating impairment of protein function. Conclusion: The T26248G is a sense mutation, which is apparently correlated with changes in the physicochemical properties of the Nsun7 proteins (e.g. molecular weight, aliphatic index, instability, hydrophobic index, protein folding) and sperm motility in infertile men. Furthermore, changes in binding energy compared with normal result in changes to ligand-protein interactions and impair methyltransferase activity. Molecular docking studies with residues and ligand in the binding cavity of the Nsun7 protein showed that protein from normospermic men has a better re-rank score, docking score, hydrogen bonding energy and ligand-protein interaction energy and, as such, has a more favorable interaction compared with proteins from infertile men. Because Nsun7 has a role in mitochondrial rRNA processing in post-meiotic spermatozoa, protein dysfunction leads to a general lack of translation of mRNA and proteins needed for sperm motility, causing sperm motility deficits and male infertility.
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نشانی اینترنتی http://ijfs.ir/journal/article/abstract/3892
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