Phosphorylation of Fibronectin Influences the Structural Stability of the Predicted Interchain Domain

As a key player in cell adhesion the glycoprotein fibronectin is involved in the complex mechanobiology of the extracellular matrix. Although the function of many modules in the fibronectin molecule has already been understood the structure and biological relevance of the C-terminal cross-linked region (CTXL) still remains unclear. It is known that fibronectin is only phosphorylated in the CTXL domain, but no results have been presented to date, which indicate a biological function based on this phosphorylation. For the first time, we introduce a structural model of the CTXL region in fibronectin, which we obtained by exhaustive replica exchange molecular dynamics simulations (TIGER2hs). The sampling revealed a conformational landscape of the dimerisation module and the global minimum state showed an umbrella-like module body and a conspicuous structural region with two feet. We observed that the CTXL foot region exhibits a structural stability in its physiological state, which disappears upon changes in ...