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Free keywords:
Actomyosin/chemistry/metabolism
Adenosine Triphosphate/*chemistry/*metabolism
Allosteric Regulation
Binding Sites
Cell Adhesion
Cell Movement
Enzyme Stability
Focal Adhesions
Mechanotransduction, Cellular
Microfilament Proteins/chemistry/metabolism
Models, Molecular
Molecular Conformation
Mutation
Protein Binding
Protein Interaction Domains and Motifs
Protein Serine-Threonine Kinases/*chemistry/genetics/*metabolism
Structure-Activity Relationship
Substrate Specificity
*focal adhesion
*integrin-linked kinase
*molecular dynamics
*traction force microscopy
Abstract:
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.
