6BZ3
Complex structure of FAK FAT domain and DCC P3 motif
Summary for 6BZ3
| Entry DOI | 10.2210/pdb6bz3/pdb |
| Descriptor | Focal adhesion kinase 1, Netrin receptor DCC, CALCIUM ION, ... (4 entities in total) |
| Functional Keywords | 4-helix bundle, axon guidance, focal adhesion kinase, transferase-peptide complex, membrane protein, transferase-membrane protein complex, transferase/membrane protein |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 4 |
| Total formula weight | 32958.32 |
| Authors | Xu, S.,Wang, J.-H. (deposition date: 2017-12-22, release date: 2018-04-04, Last modification date: 2023-10-04) |
| Primary citation | Xu, S.,Liu, Y.,Li, X.,Liu, Y.,Meijers, R.,Zhang, Y.,Wang, J.H. The binding of DCC-P3 motif and FAK-FAT domain mediates the initial step of netrin-1/DCC signaling for axon attraction. Cell Discov, 4:8-8, 2018 Cited by PubMed Abstract: Netrin-1 plays a key role in axon guidance through binding to its receptor, Deleted in Colorectal Cancer (DCC). The initial step of signaling inside the cell after netrin-1/DCC ligation is the binding of DCC cytoplasmic P3 motif to focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK). Here we report the crystal structure of P3/FAT complex. The helical P3 peptide interacts with a helix-swapped FAT dimer in a 2:2 ratio. Dimeric FAT binding is P3-specific and stabilized by a calcium ion. Biochemical studies showed that DCC-P3 motif and calcium ion could facilitate FAT dimerization in solution. Axon guidance assays confirm that the DCC/FAK complex is essential for netrin-1-induced chemoattraction. We propose that netrin-1/DCC engagement creates a small cluster of P3/FAT for FAK recruitment close to the cell membrane, which exerts a concerted effect with PIP2 for FAK signaling. We also compare P3/FAT binding with paxillin/FAT binding and discuss their distinct recognition specificity on a common FAT domain for axon attraction versus integrin signaling, respectively. PubMed: 29479476DOI: 10.1038/s41421-017-0008-8 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.497 Å) |
Structure validation
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