4plo
Crystal Structure of chicken Netrin-1 (LN-LE3) in complex with mouse DCC (FN4-5)
Structural highlights
FunctionDCC_MOUSE Receptor for netrin required for axon guidance. Mediates axon attraction of neuronal growth cones in the developing nervous system upon ligand binding. Its association with UNC5 proteins may trigger signaling for axon repulsion. It also acts as a dependence receptor required for apoptosis induction when not associated with netrin ligand. Implicated as a tumor suppressor gene. Publication Abstract from PubMedNetrins 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. Neural migration. Structures of netrin-1 bound to two receptors provide insight into its axon guidance mechanism.,Xu K, Wu Z, Renier N, Antipenko A, Tzvetkova-Robev D, Xu Y, Minchenko M, Nardi-Dei V, Rajashankar KR, Himanen J, Tessier-Lavigne M, Nikolov DB Science. 2014 Jun 13;344(6189):1275-9. doi: 10.1126/science.1255149. Epub 2014, May 29. PMID:24876346[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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