6VXK

Cryo-EM Structure of the full-length A39R/PlexinC1 complex

Summary for 6VXK

• Entry DOI: 10.2210/pdb6vxk/pdb
• EMDB information: 21442
• Descriptor: Semaphorin-like protein 139, Plexin-C1, 2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total)
• Functional Keywords: receptor, signaling, plexin, membrane protein
• Biological source: Ectromelia virus (strain Moscow) (ECTV); More
• Total number of polymer chains: 4
• Total formula weight: 441616.13

Authors

Kuo, Y.-C.,Chen, H.,Shang, G.,Uchikawa, E.,Tian, H.,Bai, X.,Zhang, X. (deposition date: 2020-02-22, release date: 2020-04-29, Last modification date: 2020-07-29)

Primary citation

Kuo, Y.C.,Chen, H.,Shang, G.,Uchikawa, E.,Tian, H.,Bai, X.C.,Zhang, X.
Cryo-EM structure of the PlexinC1/A39R complex reveals inter-domain interactions critical for ligand-induced activation.
Nat Commun, 11:1953-1953, 2020

PubMed Abstract: Plexins 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.

PubMed: 32327662
DOI: 10.1038/s41467-020-15862-0

Experimental method

ELECTRON MICROSCOPY (3.1 Å)