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...
| Main Authors: | , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2019
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/105829 http://hdl.handle.net/10220/48755 |
| _version_ | 1824457022295244800 |
|---|---|
| author | Tan, Hui-Foon Guan, Si-Yu Chng, Choon-Peng Ong, Li-Teng Tan, Suet-Mien Law, Alex Sai Kit |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Tan, Hui-Foon Guan, Si-Yu Chng, Choon-Peng Ong, Li-Teng Tan, Suet-Mien Law, Alex Sai Kit |
| author_sort | Tan, Hui-Foon |
| collection | NTU |
| description | 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. |
| first_indexed | 2025-02-19T04:03:23Z |
| format | Journal Article |
| id | ntu-10356/105829 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T04:03:23Z |
| publishDate | 2019 |
| record_format | dspace |
| spelling | ntu-10356/1058292023-02-28T17:06:39Z The binding interface of kindlin-2 and ILK involves Asp344/Asp352/Thr356 in kindlin-2 and Arg243/Arg334 in ILK Tan, Hui-Foon Guan, Si-Yu Chng, Choon-Peng Ong, Li-Teng Tan, Suet-Mien Law, Alex Sai Kit School of Biological Sciences Cell Adhesion Integrin-linked Kinase DRNTU::Science::Biological sciences 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. ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version 2019-06-14T04:14:13Z 2019-12-06T21:58:48Z 2019-06-14T04:14:13Z 2019-12-06T21:58:48Z 2018 Journal Article Guan, S.-Y., Chng, C.-P., Ong, L.-T., Tan, H.-F., Law, A. S. K., & Tan, S.-M. (2018). The binding interface of kindlin-2 and ILK involves Asp344/Asp352/Thr356 in kindlin-2 and Arg243/Arg334 in ILK. FEBS Letters, 592(1), 112-121. doi:10.1002/1873-3468.12938 0014-5793 https://hdl.handle.net/10356/105829 http://hdl.handle.net/10220/48755 10.1002/1873-3468.12938 en FEBS Letters © 2017 Federation of European Biochemical Societies. All rights reserved. This paper was published in FEBS Letters and is made available with permission of Federation of European Biochemical Societies. 10 p. application/pdf |
| spellingShingle | Cell Adhesion Integrin-linked Kinase DRNTU::Science::Biological sciences Tan, Hui-Foon Guan, Si-Yu Chng, Choon-Peng Ong, Li-Teng Tan, Suet-Mien Law, Alex Sai Kit The binding interface of kindlin-2 and ILK involves Asp344/Asp352/Thr356 in kindlin-2 and Arg243/Arg334 in ILK |
| title | The binding interface of kindlin-2 and ILK involves Asp344/Asp352/Thr356 in kindlin-2 and Arg243/Arg334 in ILK |
| title_full | The binding interface of kindlin-2 and ILK involves Asp344/Asp352/Thr356 in kindlin-2 and Arg243/Arg334 in ILK |
| title_fullStr | The binding interface of kindlin-2 and ILK involves Asp344/Asp352/Thr356 in kindlin-2 and Arg243/Arg334 in ILK |
| title_full_unstemmed | The binding interface of kindlin-2 and ILK involves Asp344/Asp352/Thr356 in kindlin-2 and Arg243/Arg334 in ILK |
| title_short | The binding interface of kindlin-2 and ILK involves Asp344/Asp352/Thr356 in kindlin-2 and Arg243/Arg334 in ILK |
| title_sort | binding interface of kindlin 2 and ilk involves asp344 asp352 thr356 in kindlin 2 and arg243 arg334 in ilk |
| topic | Cell Adhesion Integrin-linked Kinase DRNTU::Science::Biological sciences |
| url | https://hdl.handle.net/10356/105829 http://hdl.handle.net/10220/48755 |
| work_keys_str_mv | AT tanhuifoon thebindinginterfaceofkindlin2andilkinvolvesasp344asp352thr356inkindlin2andarg243arg334inilk AT guansiyu thebindinginterfaceofkindlin2andilkinvolvesasp344asp352thr356inkindlin2andarg243arg334inilk AT chngchoonpeng thebindinginterfaceofkindlin2andilkinvolvesasp344asp352thr356inkindlin2andarg243arg334inilk AT ongliteng thebindinginterfaceofkindlin2andilkinvolvesasp344asp352thr356inkindlin2andarg243arg334inilk AT tansuetmien thebindinginterfaceofkindlin2andilkinvolvesasp344asp352thr356inkindlin2andarg243arg334inilk AT lawalexsaikit thebindinginterfaceofkindlin2andilkinvolvesasp344asp352thr356inkindlin2andarg243arg334inilk AT tanhuifoon bindinginterfaceofkindlin2andilkinvolvesasp344asp352thr356inkindlin2andarg243arg334inilk AT guansiyu bindinginterfaceofkindlin2andilkinvolvesasp344asp352thr356inkindlin2andarg243arg334inilk AT chngchoonpeng bindinginterfaceofkindlin2andilkinvolvesasp344asp352thr356inkindlin2andarg243arg334inilk AT ongliteng bindinginterfaceofkindlin2andilkinvolvesasp344asp352thr356inkindlin2andarg243arg334inilk AT tansuetmien bindinginterfaceofkindlin2andilkinvolvesasp344asp352thr356inkindlin2andarg243arg334inilk AT lawalexsaikit bindinginterfaceofkindlin2andilkinvolvesasp344asp352thr356inkindlin2andarg243arg334inilk |