4GZA

Complex of mouse Plexin A2 - Semaphorin 3A - Neuropilin-1

Summary for 4GZA

• Entry DOI: 10.2210/pdb4gza/pdb
• Related: 4GZ8 4GZ9
• Descriptor: Plexin-A2, Semaphorin-3A, Neuropilin-1, ... (4 entities in total)
• Functional Keywords: ternary complex, multi-domain, mammalian, cell-cell signaling, glycosilation, transmembrane, signaling protein
• Biological source: Mus musculus (mouse); More
• Cellular location: Cell membrane; Single-pass type I membrane protein: P70207; Secreted: O08665; Membrane; Single-pass type I membrane protein: P97333
• Total number of polymer chains: 8
• Total formula weight: 582364.16

Authors

Janssen, B.J.C.,Malinauskas, T.,Siebold, C.,Jones, E.Y. (deposition date: 2012-09-06, release date: 2012-10-17, Last modification date: 2024-10-30)

Primary citation

Janssen, B.J.C.,Malinauskas, T.,Weir, G.A.,Cader, M.Z.,Siebold, C.,Jones, E.Y.
Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex.
Nat.Struct.Mol.Biol., 19:1293-1299, 2012

PubMed Abstract: Co-receptors add complexity to cell-cell signaling systems. The secreted semaphorin 3s (Sema3s) require a co-receptor, neuropilin (Nrp), to signal through plexin As (PlxnAs) in functions ranging from axon guidance to bone homeostasis, but the role of the co-receptor is obscure. Here we present the low-resolution crystal structure of a mouse semaphorin-plexin-Nrp complex alongside unliganded component structures. Dimeric semaphorin, two copies of plexin and two copies of Nrp are arranged as a dimer of heterotrimers. In each heterotrimer subcomplex, semaphorin contacts plexin, similar to in co-receptor-independent signaling complexes. The Nrp1s cross brace the assembly, bridging between sema domains of the Sema3A and PlxnA2 subunits from the two heterotrimers. Biophysical and cellular analyses confirm that this Nrp binding mode stabilizes a canonical, but weakened, Sema3-PlxnA interaction, adding co-receptor control over the mechanism by which receptor dimerization and/or oligomerization triggers signaling.

PubMed: 23104057
DOI: 10.1038/nsmb.2416

Experimental method

X-RAY DIFFRACTION (7 Å)