9F6S

PDZ domain in complex with the peptide from AP2-associated protein kinase 1

Summary for 9F6S

• Entry DOI: 10.2210/pdb9f6s/pdb
• Descriptor: PDZ and LIM domain protein 5, AP2-associated protein kinase 1 (3 entities in total)
• Functional Keywords: pdz; ap2; kinase;, cytosolic protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 10071.47

Authors

Benova, V.,Boura, E. (deposition date: 2024-05-02, release date: 2025-05-14, Last modification date: 2026-05-27)

Primary citation

Krocianova, D.,Dagg, A.D.,Clayton, R.A.,Potesil, D.,Fedorova, V.,Harmanec, A.,Benova, V.,Bosakova, V.,Kaufman, J.G.G.,Martinkova, P.,Alblova, M.,Kelly, B.T.,Hanakova, K.,Roudnicky, P.,Spielman, S.J.,Fric, J.,Sroubek, F.,Houser, J.,Wrobel, A.G.,Boura, E.,Owen, D.J.,Zdrahal, Z.,Kadlecova, Z.
AAK1-mediated phosphorylation of PDLIM5 and Talin1 promotes focal adhesion disassembly to accelerate cell migration.
Nat Commun, 2026

PubMed Abstract: AAK1 and BMP2K are serine/threonine kinases traditionally known for phosphorylating AP2 during clathrin-mediated endocytosis (CME), but their broader roles remained incompletely defined. Here, using motif-guided in silico, biochemical, and phosphoproteomic screens, we identify PDLIM5 and Talin1 as direct AAK1/BMP2K substrates. Despite high kinase-domain similarity, only AAK1 promotes cell migration and potentiates focal adhesion (FA) turnover. Live-cell imaging shows that AAK1 recruitment to FAs peaks as disassembly begins. The conserved AAK1 C-terminal PDZ-binding motif mediates direct, low-affinity binding to PDLIM5, providing a plausible mechanism for localized substrate access. Dynamic analyses of phospho-mimetic and phospho-null mutants support a model in which AAK1-dependent phosphorylation promotes timely release of PDLIM5 and Talin1 during FA disassembly. These findings reveal a kinase-driven contribution to FA turnover distinct from protease- and phosphatase-based mechanisms and suggest that functional divergence between AAK1 and BMP2K may provide a strategy to modulate cell migration with reduced impact on CME.

PubMed: 42082516
DOI: 10.1038/s41467-026-72501-w

Experimental method

X-RAY DIFFRACTION (1 Å)