PMID: 20727575

 

    Legend: Sugar

Title : Structural basis of semaphorin-plexin recognition and viral mimicry from Sema7A and A39R complexes with PlexinC1

Abstract :

1. Repulsive signaling by Semaphorins and Plexins is crucial for the development and homeostasis of the nervous, immune, and cardiovascular systems
2. Sema7A acts as both an immune and a neural Semaphorin through PlexinC1 , and A39R is a Sema7A mimic secreted by smallpox virus
3. We report the structures of Sema7A and A39R complexed with the Semaphorin-binding module of PlexinC1
4. Both structures show two PlexinC1 molecules symmetrically bridged by Semaphorin dimers , in which the Semaphorin and PlexinC1 beta propellers interact in an edge-on, orthogonal orientation
5. Both binding interfaces are dominated by the insertion of the Semaphorin 's 4c-4d loop into a deep groove in blade 3 of the PlexinC1 propeller
6. A39R appears to achieve Sema7A mimicry by preserving key Plexin-binding determinants seen in the mammalian Sema7A complex that have evolved to achieve higher affinity binding to the host-derived PlexinC1
7. The complex structures support a conserved Semaphorin-Plexin recognition mode and suggest that Plexins are activated by dimerization