Structural basis of filamin A functions Export

@article{citeulike:2412038, 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. 10.1083/jcb.200707073}, author = {Nakamura, Fumihiko and Osborn, Teresia M. and Hartemink, Christopher A. and Hartwig, John H. and Stossel, Thomas P.}, citeulike-article-id = {2412038}, citeulike-linkout-0 = {http://dx.doi.org/10.1083/jcb.200707073}, citeulike-linkout-1 = {http://www.jcb.org/cgi/content/abstract/179/5/1011}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18056414}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18056414}, day = {3}, doi = {10.1083/jcb.200707073}, journal = {J. Cell Biol.}, keywords = {cytoskeletal-dynamics, mechanotransduction, modular}, month = {December}, number = {5}, pages = {1011--1025}, posted-at = {2009-08-31 05:52:01}, priority = {0}, title = {Structural basis of filamin A functions}, url = {http://dx.doi.org/10.1083/jcb.200707073}, volume = {179}, year = {2007} }

TY - JOUR ID - citeulike:2412038 L3 - citeulike-article-id:2412038 N2 - 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. 10.1083/jcb.200707073 IS - 5 JF - J. Cell Biol. EP - 1025 TI - Structural basis of filamin A functions VL - 179 SP - 1011 KW - cytoskeletal-dynamics KW - mechanotransduction KW - modular AU - Nakamura, Fumihiko AU - Osborn, Teresia AU - Hartemink, Christopher AU - Hartwig, John AU - Stossel, Thomas PY - 2007/12/03/ UR - http://dx.doi.org/10.1083/jcb.200707073 ER -