Structural Basis of Semaphorin-Plexin Recognition and Viral Mimicry from Sema7A and A39R Complexes with PlexinC1

Journal Article · Mon Oct 18 04:00:00 EDT 2010 · Cell

DOI:https://doi.org/10.1016/j.cell.2010.07.040· OSTI ID:1002686

Liu, Heli; Juo, Z Sean; Shim, Ann Hye-Ryong; Focia, Pamela J; Chen, Xiaoyan; Garcia, K Christopher; He, Xiaolin ^[1]

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1. Stanford-MED

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.

• Research Organization: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
• Sponsoring Organization: USDOE
• OSTI ID: 1002686
• Journal Information: Cell, Journal Name: Cell Journal Issue: (5) ; 09, 2010 Vol. 142; ISSN 0092-8674; ISSN CELLB5
• Country of Publication: United States
• Language: ENGLISH

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60 APPLIED LIFE SCIENCES
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DIMERIZATION
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