2MSU

NMR structure of Kindlin-2 F2 339-358

Summary for 2MSU

• Entry DOI: 10.2210/pdb2msu/pdb
• NMR Information: BMRB: 25131
• Descriptor: Fermitin family homolog 2 (1 entity in total)
• Functional Keywords: focal adhesion, ilk, integrin, cell adhesion
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q96AC1
• Total number of polymer chains: 1
• Total formula weight: 2192.31

Authors

Fukuda, K.,Bledzka, K.,Yang, J.,Perera, H.D. (deposition date: 2014-08-05, release date: 2014-08-27, Last modification date: 2024-05-15)

Primary citation

Fukuda, K.,Bledzka, K.,Yang, J.,Perera, H.D.,Plow, E.F.,Qin, J.
Molecular Basis of Kindlin-2 Binding to Integrin-linked Kinase Pseudokinase for Regulating Cell Adhesion.
J.Biol.Chem., 289:28363-28375, 2014

PubMed Abstract: Integrin-linked kinase (ILK) is a distinct intracellular adaptor essential for integrin-mediated cell-extracellular matrix adhesion, cell spreading, and migration. Acting as a major docking platform in focal adhesions, ILK engages many proteins to dynamically link integrins with the cytoskeleton, but the underlying mechanism remains elusive. Here, we have characterized the interaction of ILK with kindlin-2, a key regulator for integrin bidirectional signaling. We show that human kindlin-2 binds to human ILK with high affinity. Using systematic mapping approaches, we have identified a major ILK binding site involving a 20-residue fragment (residues 339-358) in kindlin-2. NMR-based analysis reveals a helical conformation of this fragment that utilizes its leucine-rich surface to recognize the ILK pseudokinase domain in a mode that is distinct from another ILK pseudokinase domain binding protein, α-parvin. Structure-based mutational experiments further demonstrate that the kindlin-2 binding to ILK is crucial for the kindlin-2 localization to focal adhesions and cell spreading (integrin outside-in signaling) but dispensable for the kindlin-2-mediated integrin activation (integrin inside-out signaling). These data define a specific mode of the kindlin-2/ILK interaction with mechanistic implications as to how it spatiotemporally mediates integrin signaling and cell adhesion.

PubMed: 25160619
DOI: 10.1074/jbc.M114.596692

Experimental method

SOLUTION NMR