5AFB

Crystal structure of the Latrophilin3 Lectin and Olfactomedin Domains

Summary for 5AFB

• Entry DOI: 10.2210/pdb5afb/pdb
• Descriptor: LATROPHILIN-3, 2-acetamido-2-deoxy-beta-D-glucopyranose, SODIUM ION, ... (6 entities in total)
• Functional Keywords: signaling protein, adhesion, repulsion, guidance, beta propeller, olfactomedin, lectin
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 44505.59

Authors

Jackson, V.A.,del Toro, D.,Carrasquero, M.,Roversi, P.,Harlos, K.,Klein, R.,Seiradake, E. (deposition date: 2015-01-21, release date: 2015-03-18, Last modification date: 2024-10-09)

Primary citation

Jackson, V.A.,Del Toro, D.,Carrasquero, M.,Roversi, P.,Harlos, K.,Klein, R.,Seiradake, E.
Structural Basis of Latrophilin-Flrt Interaction.
Structure, 23:774-, 2015

PubMed 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.

PubMed: 25728924
DOI: 10.1016/J.STR.2015.01.013

Experimental method

X-RAY DIFFRACTION (2.16 Å)