In silico study of the effect of two N-terminal SNPs in E-cadherin protein on its structure, function, and stability

E-cadherin is a 120 kDa transmembrane protein that is encoded by CDH1 gene and involved in cell-cell adherens junctions. This protein is expressed in epithelial cells and its downregulation is related to cancer cell invasion and metastasis. There are many cancer-related polymorphisms have been observed in this gene, that some of them affect the protein structure and function. In this in silico study, we examined the effect of rs878854691 (M1I) and rs587780537 (G239R) single nucleotide polymorphisms on the structure and function of E-cadherin protein. Our analyses showed that rs878854691SNP is disease related. The PhD-SNP server showed that this SNP is neutral. Also, this substitution increased the absolute surface accessibility and results in protein instability. Analyses performed using Polyphen, PROVEAN and SNAP online servers showed that this amino acid substitution has no effect on the protein secondary structure.Similar studies on the rs878854691 polymorphism showed that this SNP is not disease-related and did not affect the surface accessibility of this region. The rs878854691 polymorphism did not affect the protein function but the MUpro showed the opposite results. On the other hand, analyses performed using Port PARAM online tool showed that this substitution results in significant decrease in protein stability in vivo, but does not affect the protein secondary structure.

کلیدواژه ها:

E-cadherin ، Single nucleotide polymorphism ، Protein structure and function ، Protein stability ، In silico