Structural basis of filamin A functions
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Open Access
- 3 December 2007
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 179 (5) , 1011-1025
- https://doi.org/10.1083/jcb.200707073
Abstract
Filamin A (FLNa) can effect orthogonal branching of F-actin and bind many cellular constituents. FLNa dimeric subunits have N-terminal spectrin family F-actin binding domains (ABDs) and an elongated flexible segment of 24 immunoglobulin (Ig) repeats. We generated a library of FLNa fragments to examine their F-actin binding to define the structural properties of FLNa that enable its various functions. We find that Ig repeats 9–15 contain an F-actin–binding domain necessary for high avidity F-actin binding. Ig repeats 16–24, where most FLNa-binding partners interact, do not bind F-actin, and thus F-actin does not compete with Ig repeat 23 ligand, FilGAP. Ig repeats 16–24 have a compact structure that suggests their unfolding may accommodate pre-stress–mediated stiffening of F-actin networks, partner binding, mechanosensing, and mechanoprotection properties of FLNa. Our results also establish the orientation of FLNa dimers in F-actin branching. Dimerization, mediated by FLNa Ig repeat 24, accounts for rigid high-angle FLNa/F-actin branching resistant to bending by thermal forces, and high avidity F-actin binding and cross-linking.Keywords
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