Understanding Periperal Membrane Protein Interactions | BPS Thematic Meeting

Understanding Peripheral Membrane Protein Interactions: Structure, Dynamics, Function and Therapy

Poster Abstracts

12-POS Board 12 CARDIOLIPIN MEMBRANES TRIGGER MYOSIN VI ACTIVATION, OLIGOMERIZATION, AND PROCESSIVE CARGO TRANSPORT Antonino Francesco Montanarella 1,2 ; Nikolas Hundt 1,2 ; Aron Venczel 1,2 ; Felix Zierhut 1,2 ; Simon Langnickel 1,2 ; Markus Kröss 1,2 ; Johannes Dietrich 1,2 ; Dario Saczko-Brack 1,2 ; Claudia Veigel 1,2 ; 1 Ludwig-Maximilians-Universität , München, Germany 2 Center for Nanoscience, München, Germany Mitochondrial damage determines cell fate, leading to mitochondrial autophagy or cellular apoptosis in health and disease. The molecular mechanisms and role of the acto-myosin cytoskeleton regulating mitochondrial clearance and membrane remodelling are critical in neurodegenerative disease progression including Alzheimer's, but remain unclear. Cardiolipin, a specialized phospholipid almost exclusively localized to the inner mitochondrial membrane, is exposed to the outer membrane upon mitochondrial damage and serves as marker for damage severity. We found a strong interaction between CL and the molecular motor myosin-VI (Myo6), which is recruited to damaged mitochondria and involved in autophagy initiation. We adapted a combination of molecular biology, biochemical and high-resolution fluorescence and interferometric light-scattering (iSCAT) techniques to reveal the structural Myo6-CL interaction sites, map Myo6-oligomerisation interfaces and investigate the Myo6 motor properties when bound to CL membranes. Based on our results, we propose a model on how Myo6 as peripheral membrane protein interacts with CL, is released from its backfolded, auto-inhibited conformation and is turned into a highly processive membrane cargo transporter, suitable for its role in autophagy.

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