PDBsum entry 5cmp

Cell adhesion

PDB id: 5cmp

Contents

Protein chains

324 a.a.

Ligands

NAG ×4

Waters ×60

PDB id:

5cmp

Name:

Cell adhesion

Title:

Human flrt3 lrr domain

Structure:

Leucine-rich repeat transmembrane protein flrt3. Chain: a, b, c, d. Fragment: unp residues 29-357. Synonym: fibronectin-like domain-containing leucine-rich transmembrane protein 3. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: flrt3, kiaa1469, unq856/pro1865. Expressed in: trichoplusia ni. Expression_system_taxid: 7111

Resolution:

2.60Å R-factor: 0.236 R-free: 0.300

Authors:

Y.Lu,G.Salzman,D.Arac

Key ref:

Y.C.Lu et al. (2015). Structural Basis of Latrophilin-FLRT-UNC5 Interaction in Cell Adhesion. Structure, 23, 1678-1691. PubMed id: 26235030 DOI: 10.1016/j.str.2015.06.024

Date:

17-Jul-15 Release date: 12-Aug-15

Protein chains

Q9NZU0  (FLRT3_HUMAN) -  Leucine-rich repeat transmembrane protein FLRT3 from Homo sapiens

Seq: 649 a.a.

Struc: 324 a.a.

DOI no: 10.1016/j.str.2015.06.024

Structure 23:1678-1691 (2015)

PubMed id: 26235030

Structural Basis of Latrophilin-FLRT-UNC5 Interaction in Cell Adhesion.

Y.C.Lu, O.V.Nazarko, R.Sando, G.S.Salzman, T.C.Südhof, D.Araç.

ABSTRACT

Fibronectin leucine-rich repeat transmembrane proteins (FLRTs) are cell-adhesion molecules with emerging functions in cortical development and synapse formation. Their extracellular regions interact with latrophilins (LPHNs) to mediate synapse development, and with Uncoordinated-5 (UNC5)/netrin receptors to control the migration of neurons in the developing cortex. Here, we present the crystal structures of FLRT3 in isolation and in complex with LPHN3. The LPHN3/FLRT3 structure reveals that LPHN3 binds to FLRT3 at a site distinct from UNC5. Structure-based mutations specifically disrupt LPHN3/FLRT3 binding, but do not disturb their interactions with other proteins or their cell-membrane localization. Thus, they can be used as molecular tools to dissect the functions of FLRTs and LPHNs in vivo. Our results suggest that UNC5 and LPHN3 can simultaneously bind to FLRT3, forming a trimeric complex, and that FLRT3 may form transsynaptic complexes with both LPHN3 and UNC5. These findings provide molecular insights for understanding the role of cell-adhesion proteins in synapse function.