Under tension, ATP shifts the balance from rupture of the complex to protein unfolding, indicating that ATP increases the force threshold required for focal adhesion disassembly. Disrupting this network by mutation impedes parvin binding, focal adhesion stabilization, force generation, and thus migration. We identify two key salt-bridge–forming arginines within the allosteric, ATP-dependent force-propagation network of ILK. Here, we apply force–probe molecular-dynamics simulations of human ILK: α-parvin coupled to traction force microscopy to explore ILK mechanotransducing functions. Adhesions are dynamically assembled and disassembled in response to extrinsic and intrinsic forces, but how the essential adhesion component integrin-linked kinase (ILK) dynamically responds to mechanical force and what role adenosine triphosphate (ATP) bound to this pseudokinase plays remain elusive. Focal adhesions link the actomyosin cytoskeleton to the extracellular matrix regulating cell adhesion, shape, and migration.
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