Structural basis of latrophilin-FLRT interaction

Structure
Verity A JacksonElena Seiradake

Abstract

Latrophilins, receptors for spider venom α-latrotoxin, are adhesion type G-protein-coupled receptors with emerging functions in synapse development. The N-terminal region binds the endogenous cell adhesion molecule FLRT, a major regulator of cortical and synapse development. We present crystallographic data for the mouse Latrophilin3 lectin and olfactomedin-like (Olf) domains, thereby revealing the Olf β-propeller fold and conserved calcium-binding site. We locate the FLRT-Latrophilin binding surfaces by a combination of sequence conservation analysis, point mutagenesis, and surface plasmon resonance experiments. In stripe assays, we show that wild-type Latrophilin3 and its high-affinity interactor FLRT2, but not the binding-impaired mutants we generated, promote HeLa cell adhesion. In contrast, cortical neurons expressing endogenous FLRTs are repelled by wild-type Latrophilin3 and not by the binding-impaired mutant. Taken together, we present molecular level insights into Latrophilin structure, its FLRT-binding mechanism, and a role for Latrophilin and FLRT that goes beyond a simply adhesive interaction.

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Citations

Apr 20, 2016·Nature Communications·Verity A JacksonElena Seiradake
Jul 29, 2016·Nature Reviews. Neuroscience·Tobias LangenhanKelly R Monk
Aug 19, 2016·Journal of Human Genetics·Jacklyn N HellwegeDonald W Bowden
Sep 1, 2016·Annual Review of Cell and Developmental Biology·Elena SeiradakeRüdiger Klein
Nov 5, 2016·Neuroscience Research·Reiko T RoppongiTabrez J Siddiqui
Aug 1, 2019·Annals of the New York Academy of Sciences·Nicole ScholzTorsten Schöneberg
Apr 2, 2019·Frontiers in Physiology·Suvi JauhiainenSeppo Ylä-Herttuala
Apr 24, 2015·The Journal of Biological Chemistry·Matti F PronkerBert J C Janssen
Nov 16, 2019·BMC Molecular and Cell Biology·Matti F PronkerBert J C Janssen
Jul 13, 2019·Frontiers in Neuroscience·J Peter H Burbach, Dimphna H Meijer
Mar 28, 2019·Frontiers in Neuroscience·Torsten Schöneberg, Simone Prömel
Jul 30, 2019·Frontiers in Neuroscience·Ana L Moreno-SalinasAntony A Boucard
May 28, 2019·Frontiers in Neuroscience·Luciane V SitaJackson C Bittencourt
Jan 12, 2020·Nature Communications·Katherine LeonDemet Araç
Oct 13, 2020·Frontiers in Cell and Developmental Biology·Claudia Peregrina, Daniel Del Toro
Feb 2, 2021·Frontiers in Cell and Developmental Biology·Satoru YamagishiKohji Sato
Feb 21, 2019·Current Opinion in Structural Biology·Atsushi Yamagata, Shuya Fukai
Aug 22, 2020·Current Opinion in Neurobiology·Joelle M Dorskind, Alex L Kolodkin
Jan 1, 2021·Current Opinion in Neurobiology·Rüdiger Klein, Ronald Jeroen Pasterkamp
Nov 5, 2021·Proceedings of the National Academy of Sciences of the United States of America·Yuchen WangKirill A Martemyanov
Nov 9, 2021·Frontiers in Molecular Neuroscience·Juntan LiSatoru Yamagishi
Nov 4, 2021·The FEBS Journal·Ines LiebscherSimone Prömel

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Methods Mentioned

BETA
nuclear magnetic resonance
X-ray
NMR
glycosylation
chips
chip

Software Mentioned

Autobuster
Coot
Autosharp
Xia2

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