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ATP allosterically stabilizes integrin-linked kinase for efficient force generation.

Isabel M Martin1, Michele M Nava2,3,4,5,6, Sara A Wickström2,3,4,5,6

  • 1Molecular Biomechanics, Heidelberg Institute for Theoretical Studies, 69118 Heidelberg, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|March 8, 2022
PubMed
Summary
This summary is machine-generated.

Adenosine triphosphate (ATP) binding stabilizes the pseudokinase integrin-linked kinase (ILK), enhancing its mechanosensory function. This ATP-dependent stabilization improves cell migration and focal adhesion complex stability.

Keywords:
focal adhesionintegrin-linked kinasemolecular dynamicstraction force microscopy

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Biophysics

Background:

  • Integrin-linked kinase (ILK) is a pseudokinase crucial for focal adhesions.
  • ILK mediates signal transduction between the extracellular matrix and the cell.
  • The precise role of ATP binding and ILK's mechanosensory function remain unclear.

Purpose of the Study:

  • To elucidate the molecular functions of ILK, focusing on ATP binding and mechanosensory properties.
  • To investigate how ATP binding influences ILK structure and function within focal adhesions.
  • To determine the cellular consequences of ATP-dependent ILK activity.

Main Methods:

  • Molecular-dynamics simulations were employed to model ILK behavior.
  • Cell biology techniques were used to assess ILK function in cellular contexts.
  • Combined computational and experimental approaches were utilized.

Main Results:

  • ATP binding significantly enhances the structural stability of ILK.
  • ATP binding allosterically modulates the interaction between ILK and its binding partner, parvin.
  • ILK's mechanoresistance and ability to stabilize focal adhesions are increased by ATP binding.
  • Efficient cell migration and traction force generation are facilitated by ATP-bound ILK.

Conclusions:

  • ATP binding is critical for the structural integrity and mechanosensory function of ILK.
  • The findings reveal a novel role for ATP in regulating pseudokinase activity at focal adhesions.
  • ATP-dependent ILK function is essential for cellular processes like migration and adhesion.