3IXE

Structural basis of competition between PINCH1 and PINCH2 for binding to the ankyrin repeat domain of integrin-linked kinase

Summary for 3IXE

• Entry DOI: 10.2210/pdb3ixe/pdb
• Descriptor: Integrin-linked protein kinase, LIM and senescent cell antigen-like-containing domain protein 2, ZINC ION, ... (4 entities in total)
• Functional Keywords: ilk, integrin-linked kinase, pinch, lim, ankyrin repeat, ank, ipp, integrin-mediated signaling, ank repeat, lim domain, zinc, atp-binding, cell junction, cell membrane, kinase, membrane, nucleotide-binding, phosphoprotein, serine/threonine-protein kinase, transferase, alternative splicing, metal-binding, nucleus, signaling protein-signaling protein complex, signaling protein/signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cell junction, focal adhesion: Q13418; Nucleus (Potential): Q7Z4I7
• Total number of polymer chains: 2
• Total formula weight: 28865.16

Authors

Chiswell, B.P.,Stiegler, A.L.,Boggon, T.J.,Calderwood, D.A. (deposition date: 2009-09-03, release date: 2009-12-15, Last modification date: 2023-09-06)

Primary citation

Chiswell, B.P.,Stiegler, A.L.,Razinia, Z.,Nalibotski, E.,Boggon, T.J.,Calderwood, D.A.
Structural basis of competition between PINCH1 and PINCH2 for binding to the ankyrin repeat domain of integrin-linked kinase.
J.Struct.Biol., 170:157-163, 2010

PubMed Abstract: Formation of a heterotrimeric IPP complex composed of integrin-linked kinase (ILK), the LIM domain protein PINCH, and parvin is important for signaling through integrin adhesion receptors. Mammals possess two PINCH genes that are expressed simultaneously in many tissues. PINCH1 and PINCH2 have overlapping functions and can compensate for one another in many settings; however, isoform-specific functions have been reported and it is proposed that association with a PINCH1- or PINCH2-containing IPP complex may provide a bifurcation point in integrin signaling promoting different cellular responses. Here we report that the LIM1 domains of PINCH1 and PINCH2 directly compete for the same binding site on the ankyrin repeat domain (ARD) of ILK. We determined the 1.9A crystal structure of the PINCH2 LIM1 domain complexed with the ARD of ILK, and show that disruption of this interface by point mutagenesis reduces binding in vitro and alters localization of PINCH2 in cells. These studies provide further evidence for the role of the PINCH LIM1 domain in association with ILK and highlight direct competition as one mechanism for regulating which PINCH isoform predominates in IPP complexes. Differential regulation of PINCH1 and PINCH2 expression may therefore provide a means for altering cellular integrin signaling pathways.

PubMed: 19963065
DOI: 10.1016/j.jsb.2009.12.002

Experimental method

X-RAY DIFFRACTION (1.9 Å)