Structural Basis of Semaphorin-Plexin Recognition and Viral Mimicry from Sema7A and A39R Complexes with PlexinC1
| Autor: | Z. Sean Juo, Heli Liu, K. Christopher Garcia, Xiaoyan Chen, Pamela J. Focia, Ann Hye Ryong Shim, Xiaolin He |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Models
Molecular animal structures PROTEINS Sema domain Viral protein Molecular Sequence Data Vaccinia virus Sequence alignment Semaphorins Crystallography X-Ray GPI-Linked Proteins medicine.disease_cause MOLNEURO Article General Biochemistry Genetics and Molecular Biology Viral Proteins 03 medical and health sciences 0302 clinical medicine Semaphorin Antigens CD medicine Humans Amino Acid Sequence Smallpox virus Peptide sequence 030304 developmental biology 0303 health sciences biology Biochemistry Genetics and Molecular Biology(all) Molecular Mimicry Plexin Molecular biology 3. Good health Cell biology Molecular mimicry nervous system embryonic structures biology.protein Receptors Virus sense organs Protein Multimerization biological phenomena cell phenomena and immunity Sequence Alignment 030217 neurology & neurosurgery |
| Zdroj: | Cell. 142:749-761 |
| ISSN: | 0092-8674 |
| Popis: | SummaryRepulsive 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 β 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|