4gza
Complex of mouse Plexin A2 - Semaphorin 3A - Neuropilin-1
Structural highlights
FunctionPLXA2_MOUSE Coreceptor for SEMA3A and SEMA6A. Necessary for signaling by SEMA6A and class 3 semaphorins and subsequent remodeling of the cytoskeleton. Plays a role in axon guidance, invasive growth and cell migration. Class 3 semaphorins bind to a complex composed of a neuropilin and a plexin. The plexin modulates the affinity of the complex for specific semaphorins, and its cytoplasmic domain is required for the activation of down-stream signaling events in the cytoplasm.[1] [2] [3] Publication Abstract from PubMedCo-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. Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex.,Janssen BJ, Malinauskas T, Weir GA, Cader MZ, Siebold C, Jones EY Nat Struct Mol Biol. 2012 Dec;19(12):1293-9. doi: 10.1038/nsmb.2416. Epub 2012, Oct 28. PMID:23104057[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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