6MIB

Crystal structure of the ILK ATP-binding deficient mutant (L207W)/alpha-parvin core complex

Summary for 6MIB

• Entry DOI: 10.2210/pdb6mib/pdb
• Descriptor: Integrin-linked protein kinase, Alpha-parvin (3 entities in total)
• Functional Keywords: pseudokinase, protein complex, cell adhesion
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 45888.14

Authors

Fukuda, K.,Qin, J. (deposition date: 2018-09-19, release date: 2018-11-07, Last modification date: 2024-03-13)

Primary citation

Vaynberg, J.,Fukuda, K.,Lu, F.,Bialkowska, K.,Chen, Y.,Plow, E.F.,Qin, J.
Non-catalytic signaling by pseudokinase ILK for regulating cell adhesion.
Nat Commun, 9:4465-4465, 2018

PubMed Abstract: Dynamic communication between integrin-containing complexes (focal adhesions, FAs) and actin filaments is critical for regulating cell adhesion. Pseudokinase ILK plays a key role in this process but the underlying mechanism remains highly elusive. Here we show that by recruiting FA adaptors PINCH and Parvin into a heterotrimeric complex (IPP), ILK triggers F-actin filament bundling - a process known to generate force/mechanical signal to promote cytoskeleton reassembly and dynamic cell adhesion. Structural, biochemical, and functional analyses revealed that the F-actin bundling is orchestrated by two previously unrecognized WASP-Homology-2 actin binding motifs within IPP, one from PINCH and the other from Parvin. Strikingly, this process is also sensitized to Mg-ATP bound to the pseudoactive site of ILK and its dysregulation severely impairs stress fibers formation, cell spreading, and migration. These data identify a crucial mechanism for ILK, highlighting its uniqueness as a pseudokinase to transduce non-catalytic signal and regulate cell adhesion.

PubMed: 30367047
DOI: 10.1038/s41467-018-06906-7

Experimental method

X-RAY DIFFRACTION (1.8 Å)