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.
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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
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Acknowledgments
Authors gratefully acknowledge the management of Vellore Institute of Technology University for providing the facilities to carry out this work. We thank the anonymous reviewers for their helpful comments and critical reading of the manuscript.
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Balu K., Rajendran, V., Sethumadhavan, R. et al. Investigation of Binding Phenomenon of NSP3 and p130Cas Mutants and Their Effect on Cell Signalling. Cell Biochem Biophys 67, 623–633 (2013). https://doi.org/10.1007/s12013-013-9551-6
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DOI: https://doi.org/10.1007/s12013-013-9551-6