The structural basis of integrin-linked kinase-PINCH interactions.
The heterotrimeric complex between integrin-linked kinase (ILK), PINCH, and parvin is an essential signaling platform, serving as a convergence point for integrin and growth-factor signaling and regulating cell adhesion, spreading, and migration. We report a 1.6-A crystal structure of the ILK ankyrin repeat domain bound to the PINCH1 LIM1 domain, revealing the molecular basis of ILK-PINCH interactions and providing a structural description of this region of ILK. This structure identifies 5 ankyrin repeats in ILK, explains previous deletion mutagenesis data, permits identification of ILK and PINCH1 point mutations that disrupt the interaction, shows how zincs are coordinated by PINCH1 LIM1, and suggests that conformational flexibility and twisting between the 2 zinc fingers within the LIM1 domain may be important for ILK binding. These data provide an atomic-resolution description of a key interaction in the ILK-PINCH-parvin scaffolding complex.
Chiswell
Brian P
BP
Department of Pharmacology, Yale Cancer Center and Interdepartmental Program in Vascular Biology and Transplantation, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
Zhang
Rong
R
Murphy
James W
JW
Boggon
Titus J
TJ
Calderwood
David A
DA
D048868:Adaptor Proteins, Signal Transducing; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D017354:Point Mutation; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary / Q000502:physiology; D015032:Zinc / Q000737:chemistry* / Q000378:metabolism; D016335:Zinc Fingers / Q000502:physiology; D000099200:Scaffold Protein ILK
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D015032:Zinc; D000099200:Scaffold Protein ILK; C088088:LIMS1 protein, human