Cell Biochemistry and Biophysics

, Volume 67, Issue 2, pp 623–633

Investigation of Binding Phenomenon of NSP3 and p130Cas Mutants and Their Effect on Cell Signalling

  • Balu K.
  • Vidya Rajendran
  • Rao Sethumadhavan
  • Rituraj Purohit
Original Paper

Abstract

Members of the novel SH2-containing protein (NSP3) and Crk-associated substrate (p130Cas) protein families form a multi-domain signalling platforms that mediate cell signalling process. We analysed the damaging consequences of three mutations, each from NSP3 (NSP3L469R, NSP3L623E, NSP3R627E) and p130Cas (p130CasF794R, p130CasL787E, p130CasD797R) protein with respect to their native biological partners. Mutations depicted notable loss in interaction affinity towards their corresponding biological partners. NSP3L469R and p130CasD797R mutations were predicted as most prominent in docking analysis. Molecular dynamics (MD) studies were conducted to evaluate structural consequences of most prominent mutation in NSP3 and p130Cas obtained from the docking analysis. MD analysis confirmed that mutation in NSP3L469R and p130CasD797R showed significant structural deviation, changes in conformations and increased flexibility, which in turn affected the binding affinity with their biological partners. Moreover, the root mean square fluctuation has indicated a rise in fluctuation of residues involved in moderate interaction acquired between the NSP3 and p130Cas. It has significantly affected the binding interaction in mutant complexes. The results obtained in this work present a detailed overview of molecular mechanisms involved in the loss of cell signalling associated with NSP3 and p130Cas protein.

Keywords

Cell signalling Flexibility Binding affinity Interactions Hydrogen bonds Molecular dynamics 

Abbreviations

BCAR1

Breast cancer anti-oestrogen resistance protein 1

BSA

Buried surface area

Crk

Cysteine-rich receptor like kinases

FAT

Focal adhesion target

Rg

Radius of gyration

SASA

Solvent accessible surface area

Supplementary material

12013_2013_9551_MOESM1_ESM.tif (313 kb)
Supplementary material 1 (TIFF 313 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Balu K.
    • 1
  • Vidya Rajendran
    • 1
  • Rao Sethumadhavan
    • 1
  • Rituraj Purohit
    • 1
    • 2
  1. 1.Bioinformatics Division, School of Bio Sciences and TechnologyVellore Institute of Technology UniversityVelloreIndia
  2. 2.Human Genetics FoundationTorinoItaly

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