ISSN:
1549-960X
Content:
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 dimerization module, and the global minimum state showed an umbrella-like module body and 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 the phosphorylation state. Thus, our in silico studies enabled us to show that the flexibility of the CTXL region is guided by phosphorylation. These results indicate an in vivo function of the CTXL domain in protein binding and cell adhesion, which is controlled by phosphorylation
Note:
Gesehen am 03.04.2023
In:
Journal of chemical information and modeling, Washington, DC : American Chemical Society, 2005, 59(2019), 10, Seite 4383-4392, 1549-960X
In:
volume:59
In:
year:2019
In:
number:10
In:
pages:4383-4392
Language:
English
DOI:
10.1021/acs.jcim.9b00555
Author information:
Ohler, Bastian 1981-
Author information:
Brüggemann, Dorothea 1981-
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