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

• Main Authors: Tan, Hui-Foon, Guan, Si-Yu, Chng, Choon-Peng, Ong, Li-Teng, Tan, Suet-Mien, Law, Alex Sai Kit
• Other Authors: School of Biological Sciences
• Format: Article
• Language: English
• Published: 2019
• Subjects: Cell Adhesion; Integrin-linked Kinase; DRNTU::Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/105829; http://hdl.handle.net/10220/48755
• Institution: Nanyang Technological University

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.