Title : Crystal structure of the extracellular
cholinesterase-like
domain from
neuroligin-2
Abstract :
- Neuroligins (NLs) are catalytically inactive members of a family of cholinesterase-like transmembrane proteins that mediate cell adhesion at neuronal synapses
- Postsynaptic neuroligins engage in Ca2 +-dependent transsynaptic interactions via their extracellular cholinesterase domain with presynaptic neurexins (NRXs)
- These interactions may be regulated by two short splice insertions (termed A and B) in the NL cholinesterase domain
- Here, we present the 3.3-A crystal structure of the ectodomain from NL2 containing splice insertion A (NL2A)
- The overall structure of NL2A resembles that of cholinesterases, but several structural features are unique to the NL proteins
- First, structural elements surrounding the esterase active-site region differ significantly between active esterases and NL2A
- On the opposite surface of the NL2A molecule, the positions of the A and B splice insertions identify a candidate NRX interaction site of the NL protein
- Finally, sequence comparisons of NL isoforms allow for mapping the location of residues of previously identified mutations in NL3 and NL4 found in patients with autism spectrum disorders
- Overall, the NL2 structure promises to provide a valuable model for dissecting NL isoform- and synapse-specific functions