4OVE

X-ray Crystal Structure of Mouse Netrin-1

Summary for 4OVE

• Entry DOI: 10.2210/pdb4ove/pdb
• Descriptor: Netrin-1, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (7 entities in total)
• Functional Keywords: similar to laminin gamma-1, domain vi: beta-sandwich jelly-roll, domains v-1, v-2, v-3: laminin-type epidermal growth factor, structural calcium, axon guidance cue, survival factor, neogenin, dcc, unc5a, unc5b, unc5c, unc5d, dscam, extracellular matrix, apoptosis
• Biological source: Mus musculus (mouse)
• Total number of polymer chains: 1
• Total formula weight: 50626.25

Authors

Meier, M.,Nikodemus, D.,Reuten, R.,Patel, T.R.,Orriss, G.,Okun, N.,Koch, M.,Stetefeld, J. (deposition date: 2014-02-21, release date: 2015-02-25, Last modification date: 2024-10-30)

Primary citation

Grandin, M.,Meier, M.,Delcros, J.G.,Nikodemus, D.,Reuten, R.,Patel, T.R.,Goldschneider, D.,Orriss, G.,Krahn, N.,Boussouar, A.,Abes, R.,Dean, Y.,Neves, D.,Bernet, A.,Depil, S.,Schneiders, F.,Poole, K.,Dante, R.,Koch, M.,Mehlen, P.,Stetefeld, J.
Structural Decoding of the Netrin-1/UNC5 Interaction and its Therapeutical Implications in Cancers.
Cancer Cell, 29:173-185, 2016

PubMed 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.

PubMed: 26859457
DOI: 10.1016/j.ccell.2016.01.001

Experimental method

X-RAY DIFFRACTION (2.64 Å)