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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Poster Abstracts
53
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.