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PDBsum entry 3ixe
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Signaling protein/signaling protein
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PDB id
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3ixe
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References listed in PDB file
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Key reference
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Title
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Structural basis of competition between pinch1 and pinch2 for binding to the ankyrin repeat domain of integrin-Linked kinase.
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Authors
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B.P.Chiswell,
A.L.Stiegler,
Z.Razinia,
E.Nalibotski,
T.J.Boggon,
D.A.Calderwood.
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Ref.
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J Struct Biol, 2010,
170,
157-163.
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PubMed id
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Abstract
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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.
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