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

Authors

  • Vidya Rajendran
    • Bioinformatics Division, School of Bio Sciences and TechnologyVellore Institute of Technology University
  • Rituraj Purohit
    • Bioinformatics Division, School of Bio Sciences and TechnologyVellore Institute of Technology University
    • Bioinformatics Division, School of Bio Sciences and TechnologyVellore Institute of Technology University
Original Article

DOI: 10.1007/s00726-011-1108-7

Cite this article as:
Rajendran, V., Purohit, R. & Sethumadhavan, R. Amino Acids (2012) 43: 603. doi:10.1007/s00726-011-1108-7
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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 simulationLaminopathyRMSDSASA

Copyright information

© Springer-Verlag 2011