Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Poster Abstracts

4-POS Board 2 Interaction of Atypical Kinase ADCK3 with Inner Mitochondrial Membrane Models Deniz Aydin , Matteo Dal Peraro. EPFL, Lausanne, Switzerland. Mitochondria perform diverse fundamental roles in human health besides operating as “powerhouses” of cells, as they harbour a unique proteome that remains largely unexplored. A growing number of inherited metabolic diseases are associated with mitochondrial dysfunction, which necessitates the structural and functional elucidation of mitochondrial proteins. ADCK3, a member of the mitochondrial coenzyme Q synthesis machinery, is a protein that is structurally characterized but remains functionally elusive. It has a poorly understood connection to coenzyme Q biosynthesis and an inherited neurodegenerative disease (ARCA2). Molecular dynamics (MD) simulations are a powerful tool to understand and visualize the molecular mechanisms of such structurally characterized proteins. Coarse-grained (CG) force fields are specifically useful in studying protein-lipid systems owing to their higher efficiency in sampling. In this work, CG-MD simulations are performed to determine the interaction surface of ADCK3 with the inner mitochondrial membrane, which gives hints about possible interaction surfaces of ADCK3 with other members of the coenzyme Q synthesis machinery. Further identification of specific residues involved in membrane interaction, mostly through electrostatic interactions with cardiolipins, enable future experimental validation of this interaction surface through mutagenesis experiments. The identified interaction surface exposes the substrate binding pocket to the membrane, which has implications about how ADCK3 mediates functional interactions with lipids.

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