| First Author | Rybakova IN | Year | 2005 |
| Journal | J Biol Chem | Volume | 280 |
| Issue | 24 | Pages | 23018-23 |
| PubMed ID | 15826935 | Mgi Jnum | J:100310 |
| Mgi Id | MGI:3587967 | Doi | 10.1074/jbc.M502530200 |
| Citation | Rybakova IN, et al. (2005) Identification of spectrin-like repeats required for high affinity utrophin-actin interaction. J Biol Chem 280(24):23018-23 |
| abstractText | Most studies aimed at characterizing the utrophinactin interaction have focused on the amino-terminal tandem calponin homology domain. However, we recently reported evidence suggesting that spectrin-like repeats of utrophin also participate in binding to actin. Here we expressed several recombinant fragments encoding the utrophin amino-terminal domain alone or in combination with various numbers of spectrin-like repeats. We further quantitatively characterized the actin binding properties of each recombinant utrophin fragment using a high-speed sedimentation assay. To evaluate the capacity of each protein to stabilize actin filaments, we compared the effect of utrophin recombinant fragments and full-length utrophin on 6-propionyl-2-(N,N-dimethylamino)naphthalene actin depolymerization. Our results suggest that, whereas the amino-terminal domain is essential for primary interaction between utrophin and actin, spectrin-like repeats have additive effects on the affinity and stoichiometry of binding. Our data indicate that the amino-terminal domain and first 10 consecutive spectrin-like repeats recapitulate the actin binding activity of full-length utrophin more faithfully than the amino-terminal domain alone. These findings support the model for lateral association of utrophin along the actin filament and provide the molecular basis for designing the most effective utrophin 'mini-genes' for treatment of dystrophinopathies. |
