3NVQ : Molecular mechanism of guidance cue recognition

  • Heli Liu (Contributor)
  • Z. Sean Juo (Contributor)
  • Ann Hye Ryong Shim (Contributor)
  • Pamela J Focia (Contributor)
  • Xiaoyan Chen (Contributor)
  • Xiaolin He (Contributor)



Experimental Technique/Method:X-RAY DIFFRACTION
Classification:SIGNALING PROTEIN/protein binding
Release Date:2010-09-15
Deposition Date:2010-07-08
Revision Date:2011-07-13
Molecular Weight:242651.05
Macromolecule Type:Protein
Residue Count:2132
Atom Site Count:16966

Repulsive signaling by Semaphorins and Plexins is crucial for the development and homeostasis of the nervous, immune, and cardiovascular systems. Sema7A acts as both an immune and a neural Semaphorin through PlexinC1, and A39R is a Sema7A mimic secreted by smallpox virus. We report the structures of Sema7A and A39R complexed with the Semaphorin-binding module of PlexinC1. 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. 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. 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. The complex structures support a conserved Semaphorin-Plexin recognition mode and suggest that Plexins are activated by dimerization.
Date made available2010

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