11 research outputs found
Structural and Functional Evaluation of C. elegans Filamins FLN-1 and FLN-2
Filamins are long, flexible, multi-domain proteins composed of an N-terminal actin-binding domain (ABD) followed by multiple immunoglobulin-like repeats (IgFLN). They function to organize and maintain the actin cytoskeleton, to provide scaffolds for signaling components, and to act as mechanical force sensors. In this study, we used transcript sequencing and homology modeling to characterize the gene and protein structures of the C. elegans filamin orthologs fln-1 and fln-2. Our results reveal that C. elegans FLN-1 is well conserved at the sequence level to vertebrate filamins, particularly in the ABD and several key IgFLN repeats. Both FLN-1 and the more divergent FLN-2 colocalize with actin in vivo. FLN-2 is poorly conserved, with at least 23 IgFLN repeats interrupted by large regions that appear to be nematode-specific. Our results indicate that many of the key features of vertebrate filamins are preserved in C. elegans FLN-1 and FLN-2, and suggest the nematode may be a very useful model system for further study of filamin function
Fracture strength and fractographic analysis of zirconia copings treated with four experimental silane primers
Mechanical perturbation of filamin A immunoglobulin repeats 20-21 reveals potential non-equilibrium mechanochemical partner binding function
Inter-domain interactions in filamins
Filamins are multi-domain, actin cross-linking, and scaffolding proteins. In addition to the actin cross-linking function,
filamins have a role in mechanosensor signaling. The mechanosensor function is mediated by domain-domain interaction in
the C-terminal region of filamins. Recently, we have shown that there is a three-domain interaction module in the Nterminal
region of filamins, where the neighboring domains stabilize the structure of the middle domain and thereby
regulate its interaction with ligands. In this study, we have used small-angle X-ray scattering as a tool to screen for potential
domain-domain interactions in the N-terminal region. We found evidence of four domain-domain interactions with varying
flexibility. These results confirm our previous study showing that domains 3, 4, and 5 exist as a compact three domain
module. In addition, we report interactions between domains 11–12 and 14–15, which are thus new candidate sites for
mechanical regulation.peerReviewe