ATP allosterically stabilizes integrin-linked kinase for efficient force generation.
Proc Natl Acad Sci U S A
; 119(11): e2106098119, 2022 03 15.
Article
in En
| MEDLINE
| ID: mdl-35259013
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adenosine Triphosphate
/
Protein Serine-Threonine Kinases
Language:
En
Journal:
Proc Natl Acad Sci U S A
Year:
2022
Type:
Article
Affiliation country:
Germany