BPS2026 – Anisotropic membrane curvature generation by peripherin-2 in the photoreceptor outer segment disks

Peripherin-2 is a photoreceptor-specific member of the tetraspanin transmembrane protein family. Peripherin-2 plays an essential role in the morphogenesis of the photoreceptor outer segment (OS) organelles by stabilizing the highly curved rim of OS disks. The curvature of the OS disk rim is highly anisotropic. Although disk perimeters display only modest curvature in all vertebrate species documented to date (diameters ranging from ∼1 to 8 μm), rim diameters show extreme curvature (∼22–26 nm) in all cases. The exact nature of the interactions governing rim diameter remain to be known. We have recently developed novel computational methodology for determining both the magnitude and anisotropy of membrane protein spontaneous curvature. Our method infers the intrinsic curvature preference of each membrane-bound component, including proteins, from correlations of their lateral distribution and thermal undulations. To elucidate the mechanism of curvature generation, here, we apply this method to coarse-grained molecular dynamics (MD) simulations of peripherin-2 oligomers embedded in a planar membrane at low coverage. Our results indicate that peripherin-2 is able to induce significant anisotropic curvature along the disk rim diameter, which is perpendicular to the direction of experimentally observed linear polymeric chain formation.