5F28

Crystal structure of FAT domain of Focal Adhesion Kinase (FAK) bound to the transcription factor MEF2C

5F28 の概要

• エントリーDOI: 10.2210/pdb5f28/pdb
• 分子名称: MEF2C, Focal adhesion kinase 1 (3 entities in total)
• 機能のキーワード: transcription factor, kinase, cardiovascular disease, transcription, protein binding
• 由来する生物種: Mus musculus (mouse); 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 94405.41

構造登録者

Cardoso, A.C.,Ambrosio, A.L.B.,Dessen, A.,Franchini, K.G. (登録日: 2015-12-01, 公開日: 2016-07-13, 最終更新日: 2023-09-27)

主引用文献

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

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: 27427476
DOI: 10.1016/j.str.2016.06.003

実験手法

X-RAY DIFFRACTION (2.9 Å)