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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-89450-7 |
| _version_ | 1818749166234370048 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T03:59:27Z |
| format | Article |
| id | doaj.art-778ff0f482034cf3800d06584dcf9a28 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-18T03:59:27Z |
| publishDate | 2021-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-778ff0f482034cf3800d06584dcf9a282022-12-21T21:21:43ZengNature PortfolioScientific Reports2045-23222021-05-0111111310.1038/s41598-021-89450-7Structural genomics approach to investigate deleterious impact of nsSNPs in conserved telomere maintenance component 1Arunabh Choudhury0Taj Mohammad1Nikhil Samarth2Afzal Hussain3Md. Tabish Rehman4Asimul Islam5Mohamed F. Alajmi6Shailza Singh7Md. Imtaiyaz Hassan8Department of Computer Science, Jamia Millia IslamiaCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaNational Centre for Cell ScienceDepartment of Pharmacognosy, College of Pharmacy, King Saud UniversityDepartment of Pharmacognosy, College of Pharmacy, King Saud UniversityCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaDepartment of Pharmacognosy, College of Pharmacy, King Saud UniversityNational Centre for Cell ScienceCentre for Interdisciplinary Research in Basic Sciences, Jamia Millia IslamiaAbstract 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.https://doi.org/10.1038/s41598-021-89450-7 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-89450-7 |
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