ATP allosterically stabilizes integrin-linkedkinase for efficient force generation

Martin, Isabel M.; Nava, Michele M.; Wickström, Sara A.; Graeter, Frauke


SignificanceThe pseudokinase integrin-linked kinase (ILK) is a central component of focal adhesions, cytoplasmic multiprotein complexes that integrate and transduce biochemical and mechanical signals from the extracellular environment into the cell and vice versa. However, the precise molecular functions, particularly the mechanosensory properties of ILK and the significance of retained adenosine triphosphate (ATP) binding, are still unclear. Combining molecular-dynamics simulations with cell biology, we establish a role for ATP binding to pseudokinases. We find that ATP promotes the structural stability of ILK, allosterically influences the interaction between ILK and its binding partner parvin at adhesions, and enhances the mechanoresistance of this complex. On the cellular level, ATP binding facilitates efficient traction force buildup, focal adhesion stabilization, and efficient cell migration.

Keywords: focal adhesion; integrin-linked kinase; molecular dynamics; traction force microscopy.

PMID: 35259013 DOI: 10.1073/pnas.2106098119