Format

Send to

Choose Destination
Structure. 2015 Sep 1;23(9):1665-1677. doi: 10.1016/j.str.2015.06.022. Epub 2015 Jul 30.

Structural and Mechanistic Insights into the Latrophilin3-FLRT3 Complex that Mediates Glutamatergic Synapse Development.

Author information

1
Child Health Institute of New Jersey and Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers University, 89 French Street, New Brunswick, NJ 08901, USA.
2
New York Structural Biology Center, NSLSII, Brookhaven National Laboratory, Upton, NY 11973, USA.
3
Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
4
The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229, USA.
5
New York Structural Biology Center, NSLSII, Brookhaven National Laboratory, Upton, NY 11973, USA; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA.
6
Child Health Institute of New Jersey and Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers University, 89 French Street, New Brunswick, NJ 08901, USA; Department of Pediatrics, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA. Electronic address: comoleda@rwjms.rutgers.edu.

Abstract

Latrophilins (LPHNs) are adhesion-like G-protein-coupled receptors implicated in attention-deficit/hyperactivity disorder. Recently, LPHN3 was found to regulate excitatory synapse number through trans interactions with fibronectin leucine-rich repeat transmembrane 3 (FLRT3). By isothermal titration calorimetry, we determined that only the olfactomedin (OLF) domain of LPHN3 is necessary for FLRT3 association. By multi-crystal native single-wavelength anomalous diffraction phasing, we determined the crystal structure of the OLF domain. This structure is a five-bladed β propeller with a Ca(2+) ion bound in the central pore, which is capped by a mobile loop that allows the ion to exchange with the solvent. The crystal structure of the OLF/FLRT3 complex shows that LPHN3-OLF in the closed state binds with high affinity to the concave face of FLRT3-LRR with a combination of hydrophobic and charged residues. Our study provides structural and functional insights into the molecular mechanism underlying the contribution of LPHN3/FLRT3 to the development of glutamatergic synapses.

PMID:
26235031
PMCID:
PMC4930246
DOI:
10.1016/j.str.2015.06.022
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center