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Cryo-EM Structure of the full-length A39R/PlexinC1 complex
Structural highlights
Function[SEMA_ECTVM] Acts as a semaphorin-like protein and binds to host plexin C1 receptor. May alter the movement of plexin C1-expressing cells including dendritic cells, monocytes, or granulocytes in the proximity of infected cells. May also regulate host cell cytoskeleton of neighboring cells to improve viral infection.[1] [2] [PLXC1_HUMAN] Receptor for SEMA7A, for smallpox semaphorin A39R, vaccinia virus semaphorin A39R and for herpesvirus Sema protein. Binding of semaphorins triggers cellular responses leading to the rearrangement of the cytoskeleton and to secretion of IL6 and IL8 (By similarity).[3] Publication Abstract from PubMedPlexins are receptors for semaphorins that transduce signals for regulating neuronal development and other processes. Plexins are single-pass transmembrane proteins with multiple domains in both the extracellular and intracellular regions. Semaphorin activates plexin by binding to its extracellular N-terminal Sema domain, inducing the active dimer of the plexin intracellular region. The mechanism underlying this activation process of plexin is incompletely understood. We present cryo-electron microscopic structure of full-length human PlexinC1 in complex with the viral semaphorin mimic A39R. The structure shows that A39R induces a specific dimer of PlexinC1 where the membrane-proximal domains from the two PlexinC1 protomers are placed close to each other, poised to promote the active dimer of the intracellular region. This configuration is imposed by a distinct conformation of the PlexinC1 extracellular region, stabilized by inter-domain interactions among the Sema and membrane-proximal domains. Our mutational analyses support the critical role of this conformation in PlexinC1 activation. Cryo-EM structure of the PlexinC1/A39R complex reveals inter-domain interactions critical for ligand-induced activation.,Kuo YC, Chen H, Shang G, Uchikawa E, Tian H, Bai XC, Zhang X Nat Commun. 2020 Apr 23;11(1):1953. doi: 10.1038/s41467-020-15862-0. PMID:32327662[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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