Architecture of the Sema3A/PlexinA4/Neuropilin tripartite complex.

摘要: Secreted class 3 semaphorins (Sema3s) form tripartite complexes with the plexin receptor and neuropilin coreceptor, which are both transmembrane proteins that together mediate semaphorin signal for neuronal axon guidance other processes. Despite extensive investigations, overall architecture of molecular interactions in Sema3/plexin/neuropilin complex incompletely understood. Here we present cryo-EM structure a near intact extracellular region Sema3A, PlexinA4 Neuropilin 1 (Nrp1) at 3.7 A resolution. The shows large symmetric 2:2:2 assembly each subunit makes multiple others. two molecules do not interact directly, but their membrane proximal regions close to poised promote formation intracellular active dimer signaling. reveals previously unknown interface between a2b1b2 module Nrp1 Sema domain Sema3A. This interaction places top complex, far away from plasma where embed. As result, following must span distance allow connection region, suggesting an essential role long non-conserved linkers MAM semaphorin/plexin/neuropilin complex. co-receptor transduce signals Here, authors Sema3A/PlexinA4/Neuropilin1 provides further insights into among semaphorin, flexible important formation.