5AFB: Crystal Structure Of The Latrophilin3 Lectin And Olfactomedin Domains

Citation:
Abstract
Latrophilins, receptors for spider venom alpha-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 beta-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.
PDB ID: 5AFBDownload
MMDB ID: 137382
PDB Deposition Date: 2015/1/21
Updated in MMDB: 2016/03
Experimental Method:
x-ray diffraction
Resolution: 2.16  Å
Source Organism:
Similar Structures:
Biological Unit for 5AFB: tetrameric; determined by author and by software (PISA)
Molecular Components in 5AFB
Label Count Molecule
Proteins (4 molecules)
4
Latrophilin-3(Gene symbol: Adgrl3)
Molecule annotation
Chemicals (20 molecules)
1
4
2
4
3
4
4
8
* Click molecule labels to explore molecular sequence information.

Citing MMDB
.