4WNX

Netrin 4 lacking the C-terminal Domain

4WNX の概要

• エントリーDOI: 10.2210/pdb4wnx/pdb
• 分子名称: 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)
• 機能のキーワード: basement membrane, laminin binding, n-linked glycosylation, epidermal growth factor like domain, laminin binding protein
• 由来する生物種: Mus musculus (Mouse)
• 細胞内の位置: Secreted, extracellular space, extracellular matrix, basement membrane: Q9JI33
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 49644.11

構造登録者

McDougall, M.,Patel, T.,Reuten, R.,Meier, M.,Koch, M.,Stetefeld, J. (登録日: 2014-10-14, 公開日: 2016-02-10, 最終更新日: 2024-10-16)

主引用文献

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

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: 27901020
DOI: 10.1038/ncomms13515

実験手法

X-RAY DIFFRACTION (2.723 Å)