EMBO J 2007,
PMID: 17690686
Lad, Yatish; Kiema, Tiila; Jiang, Pengju; Pentikäinen, Olli T; Coles, Charlotte H; Campbell, Iain D; Calderwood, David A; Ylänne, Jari
Human filamins are large actin-crosslinking proteins composed of an N-terminal actin-binding domain followed by 24 Ig-like domains (IgFLNs), which interact with numerous transmembrane receptors and cytosolic signaling proteins. Here we report the 2.5 A resolution structure of a three-domain fragment of human filamin A (IgFLNa19-21). The structure reveals an unexpected domain arrangement, with IgFLNa20 partially unfolded bringing IgFLNa21 into close proximity to IgFLNa19. Notably the N-terminus of IgFLNa20 forms a beta-strand that associates with the CD face of IgFLNa21 and occupies the binding site for integrin adhesion receptors. Disruption of this IgFLNa20-IgFLNa21 interaction enhances filamin binding to integrin beta-tails. Structural and functional analysis of other IgFLN domains suggests that auto-inhibition by adjacent IgFLN domains may be a general mechanism controlling filamin-ligand interactions. This can explain the increased integrin binding of filamin splice variants and provides a mechanism by which ligand binding might impact filamin structure.
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Text Mining Data
Dashed line = No text mining data
Manually curated Databases
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IRef Intact Interaction:
ITGB1
—
FLNA
(physical association, pull down)
-
IRef Intact Interaction:
ITGB1
—
FLNA
(direct interaction, pull down)
-
IRef Intact Interaction:
FLNA
—
ITGB7
(direct interaction, filter binding)
-
IRef Intact Interaction:
FLNA
—
ITGB7
(direct interaction, pull down)
-
IRef Intact Interaction:
FLNA
—
ITGB7
(direct interaction, saturation binding)
-
IRef Intact Interaction:
FLNA
—
ITGB7
(physical association, pull down)
In total, 2 gene pairs are associated to this article in curated databases