The structural basis of integrin-linked kinase-PINCH interactions.

Abstract:

: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.

authors

Chiswell BP,Zhang R,Murphy JW,Boggon TJ,Calderwood DA

doi

10.1073/pnas.0811415106

subject

Has Abstract

pub_date

2008-12-30 00:00:00

pages

20677-82

issue

52

eissn

0027-8424

issn

1091-6490

pii

0811415106

journal_volume

105

pub_type

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