How the central domain of dystrophin acts to bridge F-actin to sarcolemmal lipids

Publication date: Available online 2 November 2019Source: Journal of Structural BiologyAuthor(s): Dominique Mias-Lucquin, Raphael Dos Santos Morais, Angélique Chéron, Mélanie Lagarrigue, Steve J Winder, Thomas Chenuel, Javier Pérez, Marie-Sousai Appavou, Anne Martel, Guillaume Alviset, Elisabeth Le Rumeur, Sophie Combet, Jean-François Hubert, Olivier DelalandeAbstractDystrophin is a large intracellular protein that prevents sarcolemmal ruptures by providing a mechanical link between the intracellular actin cytoskeleton and the transmembrane dystroglycan complex. Dystrophin deficiency leads to the severe muscle wasting disease Duchenne Muscular Dystrophy and the milder allelic variant, Becker Muscular Dystrophy (DMD and BMD). Previous work has shown that concomitant interaction of the actin binding domain 2 (ABD2) comprising spectrin like repeats 11 to 15 (R11-15) of the central domain of dystrophin, with both actin and membrane lipids, can greatly increase membrane stiffness. Based on a combination of SAXS and SANS measurements, mass spectrometry analysis of cross-linked complexes and interactive low-resolution simulations, we explored in vitro the molecular properties of dystrophin that allow the formation of ABD2-F-actin and ABD2-membrane model complexes. In dystrophin we identified two subdomains interacting with F-actin, one located in R11 and a neighbouring region in R12 and another one in R15, while a single lipid binding domain was identified at the C-terminal end...
Source: Journal of Structural Biology - Category: Biology Source Type: research