The binding interface of kindlin‐2 and ILK involves Asp344/Asp352/Thr356 in kindlin‐2 and Arg243/Arg334 in ILK

Focal adhesion (FA) proteins, kindlin‐2 and integrin‐linked kinase (ILK), regulate cell adhesion and migration. ILK interacts with and promotes kindlin‐2 targeting to FAs. Leu353 and Leu357 in kindlin‐2 have been reported to be important for the interaction between kindlin‐2 and ILK. However, the bi...

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Bibliographic Details
Published in:FEBS letters 2018-01, Vol.592 (1), p.112-121
Main Authors: Guan, Si‐Yu, Chng, Choon‐Peng, Ong, Li‐Teng, Tan, Hui‐Foon, Alex Law, Sai Kit, Tan, Suet‐Mien
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino Acid Substitution
cell adhesion
Cell Adhesion - genetics
Cell Adhesion - physiology
Cell Movement - genetics
Cell Movement - physiology
HeLa Cells
Humans
integrin‐linked kinase
kindlins
Membrane Proteins - chemistry
Membrane Proteins - genetics
Membrane Proteins - metabolism
Models, Molecular
Molecular Dynamics Simulation
Mutagenesis, Site-Directed
Neoplasm Proteins - chemistry
Neoplasm Proteins - genetics
Neoplasm Proteins - metabolism
Protein Interaction Domains and Motifs
Protein-Serine-Threonine Kinases - chemistry
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Recombinant Proteins - chemistry
Recombinant Proteins - genetics
Recombinant Proteins - metabolism
Static Electricity
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Summary:Focal adhesion (FA) proteins, kindlin‐2 and integrin‐linked kinase (ILK), regulate cell adhesion and migration. ILK interacts with and promotes kindlin‐2 targeting to FAs. Leu353 and Leu357 in kindlin‐2 have been reported to be important for the interaction between kindlin‐2 and ILK. However, the binding interface between kindlin‐2 and ILK remains unclear. Using molecular modeling and molecular dynamics simulations, we show that Asp344, Asp352, and Thr356 in kindlin‐2 and Arg243 and Arg334 in ILK kinase domain (KD) are important in kindlin‐2/ILK complex formation. Mutations that disrupt these interactions abrogate kindlin‐2 and ILK colocalization in HeLa cells. The interactions are direct based on data from pull‐down assays using purified recombinant kindlin‐2 F2‐pleckstrin homology and ILK KDs. These data provide additional insights into the binding interface between kindlin‐2 and ILK.
ISSN:0014-5793
1873-3468
DOI:10.1002/1873-3468.12938