Structure of the Semaphorin-3A receptor binding module

Alexander Antipenko, Juha Pekka Himanen, Klaus Van Leyen, Vincenzo Nardi-Dei, Jacob Lesniak, William A. Barton, Kanagalaghatta R. Rajashankar, Min Lu, Claudia Hoemme, Andreas W. Püschel, Dimitar B. Nikolov

Research output: Contribution to journalArticlepeer-review

125 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)589-598
Number of pages10
JournalNeuron
Volume39
Issue number4
DOIs
StatePublished - Aug 14 2003

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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