Molecular docking study on the LMNA variant (R۴۲۷C) effect in hypertrophic cardiomyopathy patient

We studied the effect of the LMNA variant (R۴۲۷C) in the TGF-β pathway in an Iranian family withhypertrophic cardiomyopathy (HCM) by Molecular docking.LMNA gene encodes lamin A and C (lamin A/C), which are intermediate filament proteins implicating indifferent cellular processes. Mutant lamin A/C may change TGF-β۱ activity in the regulation of cell cycleprogression, negatively. Therefore, cell proliferation will be stimulated in the presence of mutant lamins A/C.Molecular docking was performed using HADDOCK Web Server to investigate the binding mode betweenthe normal and mutant forms of lamin A/C and the MAN۱. Data visualization and the interactions werechecked by PyMOL and LigPlus+, respectively.In homology modeling, the structural alteration in lamin A/C R۴۲۷C mutant was revealed. Furthermore,molecular docking identified the affinity of lamin A/C and MAN۱ interaction has been reduced in presenceof R۴۲۷C, which followed by TGF-β signaling inhibition and Smad pathway reduction through sequesteringat the nuclear envelope (NE).Molecular docking analysis provided useful information of decreased binding affinity between mutant laminA/C (R۴۲۷C) and MAN۱ in the HCM disease.

کلیدواژه ها:

Hypertrophic cardiomyopathy ، TGF-β signaling pathway ، LMNA ، Molecular docking