| First Author | Song JG | Year | 2015 |
| Journal | Structure | Volume | 23 |
| Issue | 3 | Pages | 558-70 |
| PubMed ID | 25703379 | Mgi Jnum | J:247425 |
| Mgi Id | MGI:5926858 | Doi | 10.1016/j.str.2015.01.011 |
| Citation | Song JG, et al. (2015) Structural insights into Ca2+-calmodulin regulation of Plectin 1a-integrin beta4 interaction in hemidesmosomes. Structure 23(3):558-70 |
| abstractText | The mechanical stability of epithelial cells, which protect organisms from harmful external factors, is maintained by hemidesmosomes via the interaction between plectin 1a (P1a) and integrin alpha6beta4. Binding of calcium-calmodulin (Ca(2+)-CaM) to P1a together with phosphorylation of integrin beta4 disrupts this complex, resulting in disassembly of hemidesmosomes. We present structures of the P1a actin binding domain either in complex with the N-ter lobe of Ca(2+)-CaM or with the first pair of integrin beta4 fibronectin domains. Ca(2+)-CaM binds to the N-ter isoform-specific tail of P1a in a unique manner, via its N-ter lobe in an extended conformation. Structural, cell biology, and biochemical studies suggest the following model: binding of Ca(2+)-CaM to an intrinsically disordered N-ter segment of plectin converts it to an alpha helix, which repositions calmodulin to displace integrin beta4 by steric repulsion. This model could serve as a blueprint for studies aimed at understanding how Ca(2+)-CaM or EF-hand motifs regulate F-actin-based cytoskeleton. |
