ATP allosterically stabilizes integrin-linked kinase for efficient force generation

Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2106098119. doi: 10.1073/pnas.2106098119. Epub 2022 Mar 8.


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.

MeSH terms

  • Actomyosin / chemistry
  • Actomyosin / metabolism
  • Adenosine Triphosphate / chemistry*
  • Adenosine Triphosphate / metabolism*
  • Allosteric Regulation
  • Binding Sites
  • Cell Adhesion
  • Cell Movement
  • Enzyme Stability
  • Focal Adhesions
  • Mechanotransduction, Cellular
  • Microfilament Proteins / chemistry
  • Microfilament Proteins / metabolism
  • Models, Molecular
  • Molecular Conformation
  • Mutation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Protein Serine-Threonine Kinases / chemistry*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Structure-Activity Relationship
  • Substrate Specificity


  • Microfilament Proteins
  • Adenosine Triphosphate
  • Actomyosin
  • integrin-linked kinase
  • Protein Serine-Threonine Kinases