alternative conformation of Asp436 (P65) (Figure 2E, Figure S1B, related to figure 2). Hence, a joint analysis of the two crystal forms of LPHN3-OLF and the LPHN3-RBL/OLF structure reveals that Ca2+ and Na+ both contribute to the conformational stability of the central pore residues, specifically Asp332 (Ca2+) and Asp436 (Na+). These ions also contribute to a core-stabilization of the loop 316–329 through the Ca2+- Asp332-Tyr323 interaction network. However, the partial occupancy of the ions in the P65 form and the availability of the C2221 open state where the Mg2+ occupancy reached 100 %, show that they are not absolutely required for the maintenance of the overall folding of LPHN3-OLF.
