On the dimerization of subunit g

DIEGO MASONE

Mendoza

Seminario; Seminario Interno - Instituto de Histología y Embriología de Mendoza (IHEM); 2018

Instituto de Histología y Embriología de Mendoza (IHEM)

Adenosine triphosphate (ATP) synthases found in mitochondria are the central enzymes producing ATP from adenosine diphosphate (ADP) and inorganic phosphate. Subunit g is present in all mitochondrial ATP synthases and its C-terminal α-helices are known to dimerize inside the lipid bilayer. During the ATP biosynthesis the bilayer does not remain flat and its shape plays a crucial role in the protein domains binding mechanisms. Therefore, are the dimerization of membrane-embedded subunit g transmembrane helices and the deformation of the bilayer two independent events? Does one event induces or interferes with the other? Which one is first? In this work, we have performed metadynamics simulations to calculate the free energy cost to dimerize the subunit g in a flat and in a curved bilayer. Additionally, we have calculated the necessary free energy to bend the lipid bilayer in the presence and in the absence of subunit g dimer. Our results show that the two events are sequential, meaning that the presence of subunit g dimer helical domains difficult membrane bending, while the bending of the bilayer facilitates subunit g helices to dimerize.