In silico prediction of a disease-associated STIL mutant and its affect on the recruitment of centromere protein J (CENPJ)
| العنوان: | In silico prediction of a disease-associated STIL mutant and its affect on the recruitment of centromere protein J (CENPJ) |
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| المؤلفون: | Vidya Rajendran, Ambuj Kumar, Rituraj Purohit, Rao Sethumadhavan |
| المصدر: | FEBS Open Bio |
| بيانات النشر: | Wiley, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | STIL protein, Centriole, RMSF, Root-mean square fluctuation, NHbonds, Number of hydrogen bonds, In silico, Mutant, Single-nucleotide polymorphism, Locus (genetics), CENPJ, Centromere protein J, Biology, STIL, SCL/TAL1 interrupting locus, Article, General Biochemistry, Genetics and Molecular Biology, Spindle pole body, Docking, Rg, Radius of gyration, Centromere protein J, RMSD, Root-mean-square deviation, Molecular dynamics simulation, education, Genetics, education.field_of_study, SASA, Solvent-accessible surface area, MDS, Molecular dynamics simulation, nsSNPs, non-synonymous single nucleotide polymorphisms, CENPJ protein, ED, Essential dynamics, TAL1 |
| الوصف: | Human STIL (SCL/TAL1 interrupting locus) protein maintains centriole stability and spindle pole localisation. It helps in recruitment of CENPJ (Centromere protein J)/CPAP (centrosomal P4.1-associated protein) and other centrosomal proteins. Mutations in STIL protein are reported in several disorders, especially in deregulation of cell cycle cascades. In this work, we examined the non-synonymous single nucleotide polymorphisms (nsSNPs) reported in STIL protein for their disease association. Different SNP prediction tools were used to predict disease-associated nsSNPs. Our evaluation technique predicted rs147744459 (R242C) as a highly deleterious disease-associated nsSNP and its interaction behaviour with CENPJ protein. Molecular modelling, docking and molecular dynamics simulation were conducted to examine the structural consequences of the predicted disease-associated mutation. By molecular dynamic simulation we observed structural consequences of R242C mutation which affects interaction of STIL and CENPJ functional domains. The result obtained in this study will provide a biophysical insight into future investigations of pathological nsSNPs using a computational platform. Highlights ▸ A computational platform was used for pathogenic allele prediction. ▸ The Rs147744459 allele of STIL was predicted to be most associated with disease. ▸ The R242C mutation was shown to disrupt the binding affinity of STIL for CENPJ. ▸ The 3D conformation of STIL protein was drastically affected by this mutation. ▸ Loss of H-bond formation affected protein stability in the STIL R242C mutant. |
| تدمد: | 2211-5463 1477-4445 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1957ce211ca0864dec8a3f5cfc4f386cTest https://doi.org/10.1016/j.fob.2012.09.003Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1957ce211ca0864dec8a3f5cfc4f386c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22115463 14774445 |
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