Taken together, an overall association model emerges from our studies: In the unbound state, the LRR motif of FLRT3 can dimerize with low affinity (~40μM) and LPHN3-OLF loop 316–329 is dynamic in the seconds to minutes time scale. Once these domains associate, there would be strong stabilization of the LPHN3-OLF domain in the close conformation and the disruption of the FLRT3 dimerization toward a high affinity LPHN3-OLF/FLRT3-LRR complex (Figure 6A). LPHN3 is a presynaptic protein containing an OLF domain that through the central O-linked glycosylation domain the OLF domain can reach the LRR of postsynaptic FLRT3 across the synaptic cleft, where they can interact (Figure 6B) (O’Sullivan et al., 2014).
