Amino Acids

, Volume 43, Issue 2, pp 603–615

In silico investigation of molecular mechanism of laminopathy caused by a point mutation (R482W) in lamin A/C protein

  • Vidya Rajendran
  • Rituraj Purohit
  • Rao Sethumadhavan
Original Article
  • 659 Downloads

Abstract

Lamin A/C proteins are the major components of a thin proteinaceous filamentous meshwork, the lamina, that underlies the inner nuclear membrane. A few specific mutations in the lamin A/C gene cause a disease with remarkably different clinical features: FPLD, or familial partial lipodystrophy (Dunnigan-type), which mainly affects adipose tissue. Lamin A/C mutant R482W is the key variant that causes FPLD. Biomolecular interaction and molecular dynamics (MD) simulation analysis were performed to understand dynamic behavior of native and mutant structures at atomic level. Mutant lamin A/C (R482W) showed more interaction with its biological partners due to its expansion of interaction surface and flexible nature of binding residues than native lamin A/C. MD simulation clearly indicates that the flexibility of interacting residues of mutant are mainly due to less involvement in formation of inter and intramolecular hydrogen bonds. Our analysis of native and Mutant lamin A/C clearly shows that the structural and functional consequences of the mutation R482W causes FPLD. Because of the pivotal role of lamin A/C in maintaining dynamics of nuclear function, these differences likely contribute to or represent novel mechanisms in laminopathy development.

Keywords

Docking simulation Laminopathy RMSD SASA 

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Vidya Rajendran
    • 1
  • Rituraj Purohit
    • 1
  • Rao Sethumadhavan
    • 1
  1. 1.Bioinformatics Division, School of Bio Sciences and TechnologyVellore Institute of Technology UniversityVelloreIndia

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