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

Autor:	Ranaivoson FM; 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., Liu Q; New York Structural Biology Center, NSLSII, Brookhaven National Laboratory, Upton, NY 11973, USA., Martini F; 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., Bergami F; 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., von Daake S; 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., Li S; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA., Lee D; Department of Medicine, University of California, San Diego, La Jolla, CA 92093, USA., Demeler B; The University of Texas Health Science Center at San Antonio, Department of Biochemistry, San Antonio, TX 78229, USA., Hendrickson WA; 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., Comoletti D; 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.
Jazyk:	angličtina
Zdroj:	Structure (London, England : 1993) [Structure] 2015 Sep 01; Vol. 23 (9), pp. 1665-1677. Date of Electronic Publication: 2015 Jul 30.
DOI:	10.1016/j.str.2015.06.022
Abstrakt:	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. (Copyright © 2015 Elsevier Ltd. All rights reserved.)
Databáze:	MEDLINE
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