4PLN

Crystal Structure of Chicken Netrin-1 (LN-LE3) complexed with mouse Neogenin (FN4-5)

Summary for 4PLN

• Entry DOI: 10.2210/pdb4pln/pdb
• Related: 4PLM 4PLO
• Descriptor: Netrin-1, Neogenin, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: elongated, cysteine rich, glycoprotein, complex, protein binding
• Biological source: Gallus gallus (Chicken); More
• Total number of polymer chains: 4
• Total formula weight: 144014.22

Authors

Xu, K.,Nikolov, D.B. (deposition date: 2014-05-18, release date: 2014-06-18, Last modification date: 2024-10-30)

Primary citation

Xu, K.,Wu, Z.,Renier, N.,Antipenko, A.,Tzvetkova-Robev, D.,Xu, Y.,Minchenko, M.,Nardi-Dei, V.,Rajashankar, K.R.,Himanen, J.,Tessier-Lavigne, M.,Nikolov, D.B.
Neural migration. Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism.
Science, 344:1275-1279, 2014

PubMed Abstract: Netrins are secreted proteins that regulate axon guidance and neuronal migration. Deleted in colorectal cancer (DCC) is a well-established netrin-1 receptor mediating attractive responses. We provide evidence that its close relative neogenin is also a functional netrin-1 receptor that acts with DCC to mediate guidance in vivo. We determined the structures of a functional netrin-1 region, alone and in complexes with neogenin or DCC. Netrin-1 has a rigid elongated structure containing two receptor-binding sites at opposite ends through which it brings together receptor molecules. The ligand/receptor complexes reveal two distinct architectures: a 2:2 heterotetramer and a continuous ligand/receptor assembly. The differences result from different lengths of the linker connecting receptor domains fibronectin type III domain 4 (FN4) and FN5, which differs among DCC and neogenin splice variants, providing a basis for diverse signaling outcomes.

PubMed: 24876346
DOI: 10.1126/science.1255149

Experimental method

X-RAY DIFFRACTION (3.2 Å)