Structure of the Semaphorin-3A receptor binding module Journal Article
| Authors: | Antipenko, A.; Himanen, J. P.; Van Leyen, K.; Nardi-Dei, V.; Lesniak, J.; Barton, W. A.; Rajashankar, K. R.; Lu, M.; Hoemme, C.; Püschel, A. W.; Nikolov, D. B. |
| Article Title: | Structure of the Semaphorin-3A receptor binding module |
| Abstract: | The semaphorins are a large group of extracellular proteins involved in a variety of processes during development, including neuronal migration and axon guidance. Their distinctive feature is a conserved 500 amino acid semaphorin domain, a ligand-receptor interaction module also present in plexins and scatter-factor receptors. We report the crystal structure of a secreted 65 kDa form of Semaphorin-3A (Sema3A), containing the full semaphorin domain. Unexpectedly, the semaphorin fold is a variation of the β propeller topology. Analysis of the Sema3A structure and structure-based mutagenesis data identify the neuropilin binding site and suggest a potential plexin interaction site. Based on the structure, we present a model for the initiation of semaphorin signaling and discuss potential similarities with the signaling mechanisms of other β propeller cell surface receptors, such as integrins and the LDL receptor. |
| Keywords: | signal transduction; controlled study; unclassified drug; nonhuman; protein domain; animal cell; animals; mice; protein protein interaction; nerve tissue proteins; cos cells; models, theoretical; amino acid sequence; molecular sequence data; cell adhesion molecules; binding site; crystal structure; protein structure, tertiary; binding sites; protein folding; protein structure; structure analysis; mutagenesis; integrin; isoprotein; molecular model; structural homology, protein; insect cell; membrane receptor; neuropilin; priority journal; article; low density lipoprotein receptor; neuropilins; semaphorin 3a; semaphorin-3a |
| Journal Title: | Neuron |
| Volume: | 39 |
| Issue: | 4 |
| ISSN: | 0896-6273 |
| Publisher: | Cell Press |
| Date Published: | 2003-08-14 |
| Start Page: | 589 |
| End Page: | 598 |
| Language: | English |
| DOI: | 10.1016/s0896-6273(03)00502-6 |
| PUBMED: | 12925274 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 12 September 2014 -- Source: Scopus |
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