5F28
Crystal structure of FAT domain of Focal Adhesion Kinase (FAK) bound to the transcription factor MEF2C
Summary for 5F28
| Entry DOI | 10.2210/pdb5f28/pdb |
| Descriptor | MEF2C, Focal adhesion kinase 1 (3 entities in total) |
| Functional Keywords | transcription factor, kinase, cardiovascular disease, transcription, protein binding |
| Biological source | Mus musculus (mouse) More |
| Total number of polymer chains | 7 |
| Total formula weight | 94405.41 |
| Authors | Cardoso, A.C.,Ambrosio, A.L.B.,Dessen, A.,Franchini, K.G. (deposition date: 2015-12-01, release date: 2016-07-13, Last modification date: 2023-09-27) |
| Primary citation | Cardoso, A.C.,Pereira, A.H.M.,Ambrosio, A.L.B.,Consonni, S.R.,Rocha de Oliveira, R.,Bajgelman, M.C.,Dias, S.M.G.,Franchini, K.G. FAK Forms a Complex with MEF2 to Couple Biomechanical Signaling to Transcription in Cardiomyocytes. Structure, 24:1301-1310, 2016 Cited by PubMed Abstract: Focal adhesion kinase (FAK) has emerged as a mediator of mechanotransduction in cardiomyocytes, regulating gene expression during hypertrophic remodeling. However, how FAK signaling is relayed onward to the nucleus is unclear. Here, we show that FAK interacts with and regulates myocyte enhancer factor 2 (MEF2), a master cardiac transcriptional regulator. In cardiomyocytes exposed to biomechanical stimulation, FAK accumulates in the nucleus, binds to and upregulates the transcriptional activity of MEF2 through an interaction with the FAK focal adhesion targeting (FAT) domain. In the crystal structure (2.9 Å resolution), FAT binds to a stably folded groove in the MEF2 dimer, known to interact with regulatory cofactors. FAK cooperates with MEF2 to enhance the expression of Jun in cardiomyocytes, an important component of hypertrophic response to mechanical stress. These findings underscore a connection between the mechanotransduction involving FAK and transcriptional regulation by MEF2, with potential relevance to the pathogenesis of cardiac disease. PubMed: 27427476DOI: 10.1016/j.str.2016.06.003 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.9 Å) |
Structure validation
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