PDBsum entry 4v2a

Apoptosis

PDB id: 4v2a

Contents

Protein chain

248 a.a.

Ligands

NAG

Waters ×19

PDB id:

4v2a

Name:

Apoptosis

Title:

Human unc5a ectodomain

Structure:

Netrin receptor unc5a. Chain: a. Fragment: ectodomain, unp residues 1-303. Synonym: protein unc-5 homolog 1, protein unc-5 homolog a, unc5a. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: homo sapiens. Expression_system_taxid: 9606.

Resolution:

2.40Å R-factor: 0.328 R-free: 0.344

Authors:

E.Seiradake,D.Del Toro,D.Nagel,F.Cop,R.Haertl,T.Ruff,G.Seyit-Bremer, K.Harlos,E.C.Border,A.Acker-Palmer,E.Y.Jones,R.Klein

Key ref:

E.Seiradake et al. (2014). FLRT structure: balancing repulsion and cell adhesion in cortical and vascular development. Neuron, 84, 370-385. PubMed id: 25374360 DOI: 10.1016/j.neuron.2014.10.008

Date:

08-Oct-14 Release date: 05-Nov-14

Protein chain

Q6ZN44  (UNC5A_HUMAN) -  Netrin receptor UNC5A from Homo sapiens

Seq: 842 a.a.

Struc: 248 a.a.*

* PDB and UniProt seqs differ at 3 residue positions (black crosses)

DOI no: 10.1016/j.neuron.2014.10.008

Neuron 84:370-385 (2014)

PubMed id: 25374360

FLRT structure: balancing repulsion and cell adhesion in cortical and vascular development.

E.Seiradake, D.del Toro, D.Nagel, F.Cop, R.Härtl, T.Ruff, G.Seyit-Bremer, K.Harlos, E.C.Border, A.Acker-Palmer, E.Y.Jones, R.Klein.

ABSTRACT

FLRTs are broadly expressed proteins with the unique property of acting as homophilic cell adhesion molecules and as heterophilic repulsive ligands of Unc5/Netrin receptors. How these functions direct cell behavior and the molecular mechanisms involved remain largely unclear. Here we use X-ray crystallography to reveal the distinct structural bases for FLRT-mediated cell adhesion and repulsion in neurons. We apply this knowledge to elucidate FLRT functions during cortical development. We show that FLRTs regulate both the radial migration of pyramidal neurons, as well as their tangential spread. Mechanistically, radial migration is controlled by repulsive FLRT2-Unc5D interactions, while spatial organization in the tangential axis involves adhesive FLRT-FLRT interactions. Further, we show that the fundamental mechanisms of FLRT adhesion and repulsion are conserved between neurons and vascular endothelial cells. Our results reveal FLRTs as powerful guidance factors with structurally encoded repulsive and adhesive surfaces.