Article,
Structural Insights into Ca2+-Calmodulin Regulation of Plectin 1a-Integrin $B$4 Interaction in Hemidesmosomes.
Structure (London, England : 1993), 23 (3): 558--570 (March 2015)
DOI: 10.1016/j.str.2015.01.011
Abstract
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 $\alpha$6$\beta$4. Binding of calcium-calmodulin (Ca(2+)-CaM) to P1a together with phosphorylation of integrin $\beta$4 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 $\beta$4 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 $\beta$4 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.
Tags
- acid
- amino
- and
- beta4/*chemistry,mice,models
- binding,protein
- data,plectin/*chemistry,protein
- domains
- hydrophilic
- interaction
- interactions,integrin
- line
- molecular,molecular
- motifs,protein
- sequence
- sequence,animals,calmodulin/*chemistry,cell
- structure
- tertiary,rats,to_read
- tumor,crystallography
- x-ray,hemidesmosomes/*chemistry,humans,hydrophobic
