Structure of the semaphorin-3A receptor binding module.
Publication Type:Journal Article
Source:Neuron, Volume 39, Issue 4, p.589-98 (2003)
Keywords:Amino Acid Sequence, Animals, Binding Sites, Cell Adhesion Molecules, COS Cells, Mice, Models, Theoretical, Molecular Sequence Data, Nerve Tissue Proteins, Neuropilins, Protein Structure, Tertiary, Semaphorin-3A, Signal Transduction, Structural Homology, Protein
<p>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 beta 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 beta propeller cell surface receptors, such as integrins and the LDL receptor.</p>