Crystal Structure of the Extracellular Cholinesterase-Like Domain from Neuroligin-2

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Proceedings of the National Academy of Sciences of the USA

DOI:https://doi.org/10.1073/pnas.0711701105· OSTI ID:959495

Koehnke, J; Jin, X; Budreck, E; Posy, S; Scheiffele, P; Hnoig, B; Shapiro, L

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- Angstroms 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.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 959495
• Report Number(s): BNL--82481-2009-JA
• Journal Information: Proceedings of the National Academy of Sciences of the USA, Journal Name: Proceedings of the National Academy of Sciences of the USA Journal Issue: 6 Vol. 105; ISSN 0027-8424; ISSN PNASA6
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
ADHESION
CHOLINESTERASE
CRYSTAL STRUCTURE
ESTERASES
MUTATIONS
PATIENTS
PROTEINS
RESIDUES
national synchrotron light source