A comprehensive study on identifying the structural and functional SNPs of human neuronal membrane glycoprotein M6A (GPM6A)
| Autor: | Osman Ugur Sezerman, Zoya Khalid |
|---|---|
| Přispěvatelé: | Acibadem University Dspace |
| Rok vydání: | 2021 |
| Předmět: |
glycoprotein
animal structures Angiogenesis energy minimization education 030303 biophysics Neuronal membrane non-synonymous Nerve Tissue Proteins macromolecular substances Biology Polymorphism Single Nucleotide Synapse 03 medical and health sciences Structural Biology Immunity Humans GPM6A Molecular Biology chemistry.chemical_classification 0303 health sciences Membrane Glycoproteins integumentary system Glycoprotein M6A Functional snps General Medicine Cell biology chemistry protein stability embryonic structures Mutation Wound healing Glycoprotein SNPs |
| DOI: | 10.1080/07391102.2020.1751712 |
| Popis: | Glycoprotein M6A, a stress related gene, plays an important role in synapse and filopodia formation. Filopodia formation is vital for development, immunity, angiogenesis, wound healing and metastasis. In this study, structural and functional analysis of high-risk SNPs associated with Glycoprotein M6-A were evaluated using six different bioinformatics tools. Results classified T210I, T134I, Y153H, I215T, F156L, T160I, I226T, R247W, R178C, W159R, N157S and P151L as deleterious mutants that are crucial for the structure and function of the protein causing malfunction of M6-a and ultimately leads to disease development. The three-dimensional structure of wild-type M6-a and mutant M6-a were also predicted. Furthermore, the effects of high risk substitutions were also analyzed with interaction with valproic acid. Based on structural models obtained, the binding pocket of ligand bound glycoprotein M6-A structure showed few core interacting residues which are different in the mutant models. Among all substitutions, F156L showed complete loss of binding pocket when interacting with valproic acid as compared to the wild type model. Up to the best of our knowledge this is the first comprehensive study where GPM6A mutations were analyzed. The mechanism of action of GPM6A is still not fully defined which limits the understanding of functional details encoding M6-A. Our results may help enlighten some molecular aspects underlying glycoprotein M6-A. Communicated by Ramaswamy H. Sarma. |
| Databáze: | OpenAIRE |
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