We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Mechanism of Filamin A (FLNa) actin filament (F-actin) crosslinking.
- Authors
Nakamura, Fumihiko; Osborn, Teresia; Hartwig, John H.; Stossel, Thomas P.
- Abstract
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 Ctermini. 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.
- Subjects
MICROFILAMENT proteins; ACTIN; CROSSLINKING (Polymerization); CALCIUM; CALMODULIN; ELECTRON microscopes
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA993
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fasebj.21.6.a993-c