| First Author | Xu K | Year | 2014 |
| Journal | Science | Volume | 344 |
| Issue | 6189 | Pages | 1275-9 |
| PubMed ID | 24876346 | Mgi Jnum | J:211644 |
| Mgi Id | MGI:5575806 | Doi | 10.1126/science.1255149 |
| Citation | Xu K, et al. (2014) Neural migration. Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism. Science 344(6189):1275-9 |
| abstractText | 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. |
