title: Structural basis of semaphorin-plexin recognition and viral mimicry from Sema7A and A39R complexes with PlexinC1.
abstract: 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.
authors: Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors: Heli
authors: H
authors: Liu
authors: Z Sean
authors: ZS
authors: Juo
authors: Ann Hye-Ryong
authors: AH
authors: Shim
authors: Pamela J
authors: PJ
authors: Focia
authors: Xiaoyan
authors: X
authors: Chen
authors: K Christopher
authors: KC
authors: Garcia
authors: Xiaolin
authors: X
authors: He
mesh_terms: D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D058851:GPI-Linked Proteins; D006801:Humans; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D011991:Receptors, Virus / Q000737:chemistry* / Q000378:metabolism; D039961:Semaphorins / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D014616:Vaccinia virus / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D058851:GPI-Linked Proteins; D011991:Receptors, Virus; C118753:SEMA7A protein, human; D039961:Semaphorins; C112038:VESPR semaphorin receptor; D014764:Viral Proteins