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Mutational analysis on predicting the impact of high-risk SNPs in human secretary phospholipase A2 receptor (PLA2R1)

PLA2R1 is a transmembrane glycoprotein that acts as an endogenous ligand which stimulates the processes including cell proliferation and cell migration. The SNPs in PLA2R1 is associated with idiopathic membranous nephropathy which is an autoimmune kidney disorder. The present study aimed to explore...

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Autores principales: Khalid, Zoya, Almaghrabi, Omar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366643/
https://www.ncbi.nlm.nih.gov/pubmed/32678193
http://dx.doi.org/10.1038/s41598-020-68696-7
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author Khalid, Zoya
Almaghrabi, Omar
author_facet Khalid, Zoya
Almaghrabi, Omar
author_sort Khalid, Zoya
collection PubMed
description PLA2R1 is a transmembrane glycoprotein that acts as an endogenous ligand which stimulates the processes including cell proliferation and cell migration. The SNPs in PLA2R1 is associated with idiopathic membranous nephropathy which is an autoimmune kidney disorder. The present study aimed to explore the structure–function analysis of high risk SNPs in PLA2R1 by using 12 different computational tools. First the functional annotation of SNPs were carried out by sequence based tools which were further subjected to evolutionary conservation analysis. Those SNPs which were predicted as deleterious in both categories were further considered for structure based analysis. The resultant SNPs were C1096S, C545S, C664S, F1257L, F734S, I1174T, I1114T, P177S, P384S, W1198G, W1328G, W692C, W692L, W962R, Y499H. One functional domain of PLA2R1 is already modelled in PDB (6JLI), the full 3D structure of the protein was predicted using I-TASSER homology modelling tool. The stability analysis, structure superimposition, RMSD calculation and docking studies were carried out. The structural analysis predicted four mutations F734S, F1246L, I1174T, W1198G as damaging to the structure of the protein. All these mutations are occurring at the conserved region of CTL domain hence are more likely to abolish the function of the protein. Up to the best of our knowledge, this is the first study that provides in-depth and in-silico analysis of deleterious mutations on structure and function of PLA2R1.
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spelling pubmed-73666432020-07-17 Mutational analysis on predicting the impact of high-risk SNPs in human secretary phospholipase A2 receptor (PLA2R1) Khalid, Zoya Almaghrabi, Omar Sci Rep Article PLA2R1 is a transmembrane glycoprotein that acts as an endogenous ligand which stimulates the processes including cell proliferation and cell migration. The SNPs in PLA2R1 is associated with idiopathic membranous nephropathy which is an autoimmune kidney disorder. The present study aimed to explore the structure–function analysis of high risk SNPs in PLA2R1 by using 12 different computational tools. First the functional annotation of SNPs were carried out by sequence based tools which were further subjected to evolutionary conservation analysis. Those SNPs which were predicted as deleterious in both categories were further considered for structure based analysis. The resultant SNPs were C1096S, C545S, C664S, F1257L, F734S, I1174T, I1114T, P177S, P384S, W1198G, W1328G, W692C, W692L, W962R, Y499H. One functional domain of PLA2R1 is already modelled in PDB (6JLI), the full 3D structure of the protein was predicted using I-TASSER homology modelling tool. The stability analysis, structure superimposition, RMSD calculation and docking studies were carried out. The structural analysis predicted four mutations F734S, F1246L, I1174T, W1198G as damaging to the structure of the protein. All these mutations are occurring at the conserved region of CTL domain hence are more likely to abolish the function of the protein. Up to the best of our knowledge, this is the first study that provides in-depth and in-silico analysis of deleterious mutations on structure and function of PLA2R1. Nature Publishing Group UK 2020-07-16 /pmc/articles/PMC7366643/ /pubmed/32678193 http://dx.doi.org/10.1038/s41598-020-68696-7 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Khalid, Zoya
Almaghrabi, Omar
Mutational analysis on predicting the impact of high-risk SNPs in human secretary phospholipase A2 receptor (PLA2R1)
title Mutational analysis on predicting the impact of high-risk SNPs in human secretary phospholipase A2 receptor (PLA2R1)
title_full Mutational analysis on predicting the impact of high-risk SNPs in human secretary phospholipase A2 receptor (PLA2R1)
title_fullStr Mutational analysis on predicting the impact of high-risk SNPs in human secretary phospholipase A2 receptor (PLA2R1)
title_full_unstemmed Mutational analysis on predicting the impact of high-risk SNPs in human secretary phospholipase A2 receptor (PLA2R1)
title_short Mutational analysis on predicting the impact of high-risk SNPs in human secretary phospholipase A2 receptor (PLA2R1)
title_sort mutational analysis on predicting the impact of high-risk snps in human secretary phospholipase a2 receptor (pla2r1)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366643/
https://www.ncbi.nlm.nih.gov/pubmed/32678193
http://dx.doi.org/10.1038/s41598-020-68696-7
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