Figure 7

Model for the ultrastructure of the intraperiod line. Potential arrangement of P0 in the intraperiod line and lipid bilayers. Antiparallel apposing Ig-like domains interact weakly with each other through a β-strand stretch (red dotted circle; based on crystal contacts in PDB ID 1neu¹²) and form the basis of membrane stacking in the extracellular space. This arrangement results in the C-terminal end of the crystal structure to face the membrane, which logically would continue into the subsequent transmembrane helix. Additionally, the size of the antiparallel dimer is similar to the width of the intraperiod line. While the lateral Ig-like domain monomers are not necessarily in close contact with one another, P0ct anchors onto the cytoplasmic phospholipid headgroups through electrostatic interactions, gaining folding and potentially forming a stable, ordered protein lattice within the membrane, which forces P0 molecules to adjacency, including the extracellular domains. Additionally, P0ct changes the phase transition properties of the lipid bilayer, potentially influencing the stiffness and stability of PNS compact myelin, given that P0ct is capable of changing the mechanical properties of membranes in its bilayer-bound state. The given lengths in brackets match the measured dimensions from the crystal structure, cryo-EM micrographs, and SAXD.