Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1

Abstract Conserved telomere maintenance component 1 (CTC1) is an important component of the CST (CTC1-STN1-TEN1) complex, involved in maintaining the stability of telomeric DNA. Several non-synonymous single-nucleotide polymorphisms (nsSNPs) in CTC1 have been reported to cause Coats plus syndrome an...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Arunabh Choudhury, Taj Mohammad, Nikhil Samarth, Afzal Hussain, Md. Tabish Rehman, Asimul Islam, Mohamed F. Alajmi, Shailza Singh, Md. Imtaiyaz Hassan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/778ff0f482034cf3800d06584dcf9a28
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:778ff0f482034cf3800d06584dcf9a28
record_format	dspace
spelling	oai:doaj.org-article:778ff0f482034cf3800d06584dcf9a282021-12-02T15:54:59ZStructural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 110.1038/s41598-021-89450-72045-2322https://doaj.org/article/778ff0f482034cf3800d06584dcf9a282021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89450-7https://doaj.org/toc/2045-2322Abstract Conserved telomere maintenance component 1 (CTC1) is an important component of the CST (CTC1-STN1-TEN1) complex, involved in maintaining the stability of telomeric DNA. Several non-synonymous single-nucleotide polymorphisms (nsSNPs) in CTC1 have been reported to cause Coats plus syndrome and Dyskeratosis congenital diseases. Here, we have performed sequence and structure analyses of nsSNPs of CTC1 using state-of-the-art computational methods. The structure-based study focuses on the C-terminal OB-fold region of CTC1. There are 11 pathogenic mutations identified, and detailed structural analyses were performed. These mutations cause a significant disruption of noncovalent interactions, which may be a possible reason for CTC1 instability and consequent diseases. To see the impact of such mutations on the protein conformation, all-atom molecular dynamics (MD) simulations of CTC1-wild-type (WT) and two of the selected mutations, R806C and R806L for 200 ns, were carried out. A significant conformational change in the structure of the R806C mutant was observed. This study provides a valuable direction to understand the molecular basis of CTC1 dysfunction in disease progression, including Coats plus syndrome.Arunabh ChoudhuryTaj MohammadNikhil SamarthAfzal HussainMd. Tabish RehmanAsimul IslamMohamed F. AlajmiShailza SinghMd. Imtaiyaz HassanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Arunabh Choudhury Taj Mohammad Nikhil Samarth Afzal Hussain Md. Tabish Rehman Asimul Islam Mohamed F. Alajmi Shailza Singh Md. Imtaiyaz Hassan Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1
description	Abstract Conserved telomere maintenance component 1 (CTC1) is an important component of the CST (CTC1-STN1-TEN1) complex, involved in maintaining the stability of telomeric DNA. Several non-synonymous single-nucleotide polymorphisms (nsSNPs) in CTC1 have been reported to cause Coats plus syndrome and Dyskeratosis congenital diseases. Here, we have performed sequence and structure analyses of nsSNPs of CTC1 using state-of-the-art computational methods. The structure-based study focuses on the C-terminal OB-fold region of CTC1. There are 11 pathogenic mutations identified, and detailed structural analyses were performed. These mutations cause a significant disruption of noncovalent interactions, which may be a possible reason for CTC1 instability and consequent diseases. To see the impact of such mutations on the protein conformation, all-atom molecular dynamics (MD) simulations of CTC1-wild-type (WT) and two of the selected mutations, R806C and R806L for 200 ns, were carried out. A significant conformational change in the structure of the R806C mutant was observed. This study provides a valuable direction to understand the molecular basis of CTC1 dysfunction in disease progression, including Coats plus syndrome.
format	article
author	Arunabh Choudhury Taj Mohammad Nikhil Samarth Afzal Hussain Md. Tabish Rehman Asimul Islam Mohamed F. Alajmi Shailza Singh Md. Imtaiyaz Hassan
author_facet	Arunabh Choudhury Taj Mohammad Nikhil Samarth Afzal Hussain Md. Tabish Rehman Asimul Islam Mohamed F. Alajmi Shailza Singh Md. Imtaiyaz Hassan
author_sort	Arunabh Choudhury
title	Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1
title_short	Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1
title_full	Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1
title_fullStr	Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1
title_full_unstemmed	Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1
title_sort	structural genomics approach to investigate deleterious impact of nssnps in conserved telomere maintenance component 1
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/778ff0f482034cf3800d06584dcf9a28
work_keys_str_mv	AT arunabhchoudhury structuralgenomicsapproachtoinvestigatedeleteriousimpactofnssnpsinconservedtelomeremaintenancecomponent1 AT tajmohammad structuralgenomicsapproachtoinvestigatedeleteriousimpactofnssnpsinconservedtelomeremaintenancecomponent1 AT nikhilsamarth structuralgenomicsapproachtoinvestigatedeleteriousimpactofnssnpsinconservedtelomeremaintenancecomponent1 AT afzalhussain structuralgenomicsapproachtoinvestigatedeleteriousimpactofnssnpsinconservedtelomeremaintenancecomponent1 AT mdtabishrehman structuralgenomicsapproachtoinvestigatedeleteriousimpactofnssnpsinconservedtelomeremaintenancecomponent1 AT asimulislam structuralgenomicsapproachtoinvestigatedeleteriousimpactofnssnpsinconservedtelomeremaintenancecomponent1 AT mohamedfalajmi structuralgenomicsapproachtoinvestigatedeleteriousimpactofnssnpsinconservedtelomeremaintenancecomponent1 AT shailzasingh structuralgenomicsapproachtoinvestigatedeleteriousimpactofnssnpsinconservedtelomeremaintenancecomponent1 AT mdimtaiyazhassan structuralgenomicsapproachtoinvestigatedeleteriousimpactofnssnpsinconservedtelomeremaintenancecomponent1
_version_	1718385455715581952

Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1

Ejemplares similares