Force interacts with macromolecular structure in activation of TGF-β.

ABSTRACT: Integrins are adhesion receptors that transmit force across the plasma membrane between extracellular ligands and the actin cytoskeleton. In activation of the transforming growth factor-β1 precursor (pro-TGF-β1), integrins bind to the prodomain, apply force, and release the TGF-β growth factor. However, we know little about how integrins bind macromolecular ligands in the extracellular matrix or transmit force to them. Here we show how integrin α_Vβ₆ binds pro-TGF-β1 in an orientation biologically relevant for force-dependent release of TGF-β from latency. The conformation of the prodomain integrin-binding motif differs in the presence and absence of integrin binding; differences extend well outside the interface and illustrate how integrins can remodel extracellular m

SUBMITTER: Dong X 

PROVIDER: S-EPMC5586147 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature