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Exploring the effect of nsSNPs in human YPEL3 gene in cellular senescence

Abhishek Singh1, Mukesh Thakur2, Sujeet Kumar Singh3

  • 1Zoological Survey of India, New Alipore, Kolkata, 700053, India. abhisheksingh9193@gmail.com.

Scientific Reports
|September 18, 2020
PubMed

Insights

This study reveals how YPEL3 protein mutations impact cellular senescence. Specific mutations alter protein structure and flexibility, potentially affecting cancer development and offering new avenues for targeted cancer therapies.

Area of Science:

  • Biochemistry and Molecular Biology
  • Genetics and Genomics
  • Cancer Research

Background:

  • YPEL3 protein plays a role in cellular senescence in human normal and tumor cells.
  • Altered YPEL3 expression due to incidental mutations can influence its function.
  • Understanding YPEL3's structural dynamics is crucial for cancer research.

Purpose of the Study:

  • To determine the structural and functional impact of deleterious YPEL3 protein mutants.
  • To predict the effects of specific single nucleotide polymorphisms (nsSNPs) on YPEL3 protein stability and conformation.
  • To provide insights for developing precise cancer medicines.

Main Methods:

  • Protein structure prediction of native YPEL3 and five mutants (V40M, C61Y, G98R, G108S, A131T).
  • Molecular Dynamics (MD) simulations including RMSD, RMSF, Rg, h-bond, and SASA analysis.
  • In silico prediction of deleterious effects on protein stability, flexibility, and conformational changes.

Main Results:

  • The study presents the first structural model of native YPEL3 protein.
  • MD simulations indicated that variants V40M, G98R, and G108S increase protein flexibility.
  • Variant V40M was observed to increase protein compactness, while all studied variants altered the native YPEL3 conformation and structure.

Conclusions:

  • Mutations in YPEL3 can significantly alter its native structure and function related to cellular senescence.
  • These findings suggest potential mechanisms by which YPEL3 dysfunction contributes to cancer.
  • The identified nsSNPs provide targets for future in vitro and in vivo studies investigating YPEL3 protein malfunction in diseases like cancer.

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