Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism Journal Article
| Authors: | 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. |
| Article Title: | Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism |
| 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. |
| Keywords: | genetics; mouse; animal; animals; mice; mice, mutant strains; membrane proteins; cell motion; nerve growth factors; neurons; mice, inbred c57bl; physiology; c57bl mouse; chemistry; protein multimerization; nerve fiber; tumor suppressor proteins; membrane protein; ligand; cell movement; ligands; protein structure, tertiary; tumor suppressor protein; nerve cell; ultrastructure; protein tertiary structure; axons; cell surface receptor; receptors, cell surface; fibronectin; netrin 1; nerve growth factor; neogenin; fibronectins; article; dcc protein, mouse; netrin receptors; netrin-1; mutant mouse strain |
| Journal Title: | Science |
| Volume: | 344 |
| Issue: | 6189 |
| ISSN: | 0036-8075 |
| Publisher: | American Association for the Advancement of Science |
| Date Published: | 2014-06-13 |
| Start Page: | 1275 |
| End Page: | 1279 |
| Language: | English |
| DOI: | 10.1126/science.1255149 |
| PROVIDER: | scopus |
| PUBMED: | 24876346 |
| PMCID: | PMC4369087 |
| DOI/URL: | |
| Notes: | Science -- Export Date: 8 July 2014 -- CODEN: SCIEA -- Source: Scopus |
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