Feb 12 – 16, 2024
EPN Campus
Europe/Paris timezone

Asymmetric hydrophobic mismatch in assembly of ATP synthase rotor ring

Feb 13, 2024, 11:35 AM
IBS seminar room (EPN Campus)

IBS seminar room

EPN Campus

71 avenue des Martyrs 38000 Grenoble


Ivan Gushchin (Moscow Institute of Physics and Technology)


Rotary ATPases are multisubunit enzyme complexes that couple synthesis or hydrolysis of ATP molecules with transport of ions across a membrane. Their transmembrane part includes a homo- or a heterooligomer of c subunits called a c-ring, with a patch of several lipids confined inside it. Little is known about this patch; it is usually not well resolved in experimental structures, but it is clear that the lipids in it are displaced relative to the surrounding membrane. Here, we show that a protocol involving coarse-grained and atomistic molecular dynamics simulations can be used to obtain a model of the rotor ring protein-lipid assembly that fits well the experimental densities. We then study the mechanism of self-assembly of tetradecameric spinach chloroplast ATP synthase c-ring and demonstrate that c subunits display unusual asymmetric hydrophobic mismatch. Monomers and partially assembled oligomers cause a deformation of the surrounding membrane, which results in their mutual attraction. Because of asymmetry in the deformation, the subunits assume a relative orientation that favors correct assembly of higher-order oligomers and, eventually, of the whole ring. We estimate the binding energies of different oligomers and build a model for the complete assembly process of a c-ring starting from individual protomers. Presented modeling process and biophysical considerations are likely generalizable to assembly of other membrane protein complexes with high-order rotational symmetry.

Submitting to: Integrative Computational Biology workshop

Primary authors

Mr Alexander Kuzmin Ivan Gushchin (Moscow Institute of Physics and Technology)

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