4WNX
Netrin 4 lacking the C-terminal Domain
Summary for 4WNX
| Entry DOI | 10.2210/pdb4wnx/pdb |
| Descriptor | Netrin-4, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total) |
| Functional Keywords | basement membrane, laminin binding, n-linked glycosylation, epidermal growth factor like domain, laminin binding protein |
| Biological source | Mus musculus (Mouse) |
| Cellular location | Secreted, extracellular space, extracellular matrix, basement membrane: Q9JI33 |
| Total number of polymer chains | 1 |
| Total formula weight | 49644.11 |
| Authors | McDougall, M.,Patel, T.,Reuten, R.,Meier, M.,Koch, M.,Stetefeld, J. (deposition date: 2014-10-14, release date: 2016-02-10, Last modification date: 2024-10-16) |
| Primary citation | Reuten, R.,Patel, T.R.,McDougall, M.,Rama, N.,Nikodemus, D.,Gibert, B.,Delcros, J.G.,Prein, C.,Meier, M.,Metzger, S.,Zhou, Z.,Kaltenberg, J.,McKee, K.K.,Bald, T.,Tuting, T.,Zigrino, P.,Djonov, V.,Bloch, W.,Clausen-Schaumann, H.,Poschl, E.,Yurchenco, P.D.,Ehrbar, M.,Mehlen, P.,Stetefeld, J.,Koch, M. Structural decoding of netrin-4 reveals a regulatory function towards mature basement membranes. Nat Commun, 7:13515-13515, 2016 Cited by PubMed Abstract: Netrins, a family of laminin-related molecules, have been proposed to act as guidance cues either during nervous system development or the establishment of the vascular system. This was clearly demonstrated for netrin-1 via its interaction with the receptors DCC and UNC5s. However, mainly based on shared homologies with netrin-1, netrin-4 was also proposed to play a role in neuronal outgrowth and developmental/pathological angiogenesis via interactions with netrin-1 receptors. Here, we present the high-resolution structure of netrin-4, which shows unique features in comparison with netrin-1, and show that it does not bind directly to any of the known netrin-1 receptors. We show that netrin-4 disrupts laminin networks and basement membranes (BMs) through high-affinity binding to the laminin γ1 chain. We hypothesize that this laminin-related function is essential for the previously described effects on axon growth promotion and angiogenesis. Our study unveils netrin-4 as a non-enzymatic extracellular matrix protein actively disrupting pre-existing BMs. PubMed: 27901020DOI: 10.1038/ncomms13515 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.723 Å) |
Structure validation
Download full validation report
