Structural features and lipid binding domain of tubulin on biomimetic mitochondrial membranes
Résumé
Significance Tubulin has emerged as a highly unexpected component of mitochondrial membranes involved in regulation of membrane permeability. This discovery has reawakened interest in the nature of the tubulin–membrane interaction to answer a new question: How does tubulin, a cytosolic protein famous for its role in microtubule structure and dynamics, come to target mitochondrial membranes? Here, using a combination of five biophysical methods, we study peripheral binding of tubulin to biomimetic membranes of different lipid compositions. We conclude that tubulin distinguishes between lamellar and nonlamellar lipids through a highly conserved amphipathic binding motif. Specifically, α-tubulin targets cell and organelle membranes by sensing lipid-packing defects via an amphipathic α-helix, with broad consequences for both normal cellular function and disease.