Premium
Mechanism of Filamin A (FLNa) actin filament (F‐actin) crosslinking
Author(s) -
Nakamura Fumihiko,
Osborn Teresia,
Hartwig John H.,
Stossel Thomas P.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a993-c
Subject(s) - flna , filamin , actin , microbiology and biotechnology , actin remodeling of neurons , actin binding protein , chemistry , biophysics , actin cytoskeleton , biology , cytoskeleton , biochemistry , cell
FLNa is a scaffold with multiple binding partners and, by promoting orthogonal F‐actin branching, is a potent F‐actin gelation factor. Subunits composing this elongated homodimeric molecule have N‐terminal F‐actin‐binding domains (ABDs) connected to 24 Ig‐like repeats that dimerize at C‐terminal repeat 24. We report that deletion of ABDs abolishes F‐actin gelation activity, explaining how calcium‐calmodulin, acting through this domain, dissociates FLNa from F‐actin. FLNa repeats 1 to 15 enhance the affinity of FLNa subunits for F‐actin 25‐fold; adding repeats 16–23, where most FLNa binding partners interact, barely increases affinity. Dimerization, however, increases the avidity by 1000‐fold. Electron‐ and videomicroscopy reveal that FLNa subunits bind F‐actin laterally and interact perpendicularly at their C‐termini. These findings ascribe firm F‐actin tethering to the ABDs, repeats 1–15 and bivalency. Weak F‐actin binding by repeats 16–23 accommodates crosslink flexibility that confers unique rheological properties to FLNa‐F‐actin gels and permits partner interactions. The self‐association domains account for perpendicular F‐actin branching.