Structure of the semaphorin-3A receptor binding module

Neuron. 2003 Aug 14;39(4):589-98. doi: 10.1016/s0896-6273(03)00502-6.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • COS Cells
  • Cell Adhesion Molecules / metabolism
  • Mice
  • Models, Theoretical
  • Molecular Sequence Data
  • Nerve Tissue Proteins / metabolism
  • Neuropilins / metabolism
  • Protein Structure, Tertiary
  • Semaphorin-3A / chemistry*
  • Semaphorin-3A / metabolism
  • Signal Transduction
  • Structural Homology, Protein


  • Cell Adhesion Molecules
  • Nerve Tissue Proteins
  • Neuropilins
  • Semaphorin-3A
  • plexin