PDBsum entry 4ove

Apoptosis

PDB id: 4ove

Contents

Protein chain

422 a.a.

Ligands

NAG-NAG-BMA-MAN-MAN

NAG-NAG

NAG

Metals

_CL

_CA

Waters ×97

PDB id:

4ove

Name:

Apoptosis

Title:

X-ray crystal structure of mouse netrin-1

Structure:

Netrin-1. Chain: a. Engineered: yes

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: ntn1. Expressed in: homo sapiens. Expression_system_taxid: 9606. Expression_system_cell_line: hek293. Expression_system_organ: kidney.

Resolution:

2.64Å R-factor: 0.233 R-free: 0.288

Authors:

M.Meier,D.Nikodemus,R.Reuten,T.R.Patel,G.Orriss,N.Okun,M.Koch, J.Stetefeld

Key ref:

M.Grandin et al. (2016). Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers. Cancer Cell, 29, 173-185. PubMed id: 26859457 DOI: 10.1016/j.ccell.2016.01.001

Date:

21-Feb-14 Release date: 25-Feb-15

Protein chain

O09118  (NET1_MOUSE) -  Netrin-1 from Mus musculus

Seq: 604 a.a.

Struc: 422 a.a.

DOI no: 10.1016/j.ccell.2016.01.001

Cancer Cell 29:173-185 (2016)

PubMed id: 26859457

Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers.

M.Grandin, M.Meier, J.G.Delcros, D.Nikodemus, R.Reuten, T.R.Patel, D.Goldschneider, G.Orriss, N.Krahn, A.Boussouar, R.Abes, Y.Dean, D.Neves, A.Bernet, S.Depil, F.Schneiders, K.Poole, R.Dante, M.Koch, P.Mehlen, J.Stetefeld.

ABSTRACT

Netrin-1 has been shown to be up-regulated in a fraction of human cancers as a mechanism to allow these tumors to escape the pro-apoptotic activity of some of its main dependence receptors, the UNC5 homologs (UNC5H). Here we identify the V-2 domain of netrin-1 to be important for its interaction with the Ig1/Ig2 domains of UNC5H2. We generate a humanized anti-netrin-1 antibody that disrupts the interaction between netrin-1 and UNC5H2 and triggers death of netrin-1-expressing tumor cells in vitro. We also present evidence that combining the anti-netrin-1 antibody with epidrugs such as decitabine could be effective in treating tumors showing no or modest netrin-1 expression. These results support that this antibody is a promising drug candidate.