4RML

Crystal structure of the Olfactomedin domain of latrophilin 3 in C2221 crystal form

Summary for 4RML

• Entry DOI: 10.2210/pdb4rml/pdb
• Related: 4RMK
• Descriptor: Latrophilin-3, MAGNESIUM ION, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• Functional Keywords: five-bladed beta-propeller, trans-synaptic adhesion gpcr, flrt3, central nervous system, signaling protein
• Biological source: Mus musculus (mouse)
• Cellular location: Cell membrane; Multi-pass membrane protein: Q80TS3
• Total number of polymer chains: 1
• Total formula weight: 36779.02

Authors

Ranaivoson, F.M.,Liu, Q.,Martini, F.,Bergami, F.,Von daake, S.,Li, S.,Demeler, B.,Hendrickson, W.A.,Comoletti, D. (deposition date: 2014-10-21, release date: 2015-08-19, Last modification date: 2024-10-09)

Primary citation

Ranaivoson, F.M.,Liu, Q.,Martini, F.,Bergami, F.,von Daake, S.,Li, S.,Lee, D.,Demeler, B.,Hendrickson, W.A.,Comoletti, D.
Structural and Mechanistic Insights into the Latrophilin3-FLRT3 Complex that Mediates Glutamatergic Synapse Development.
Structure, 23:1665-1677, 2015

PubMed 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.

PubMed: 26235031
DOI: 10.1016/j.str.2015.06.022

Experimental method

X-RAY DIFFRACTION (1.601 Å)