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© Springer Japan 2015. The biological activities of the semaphorins and their receptors depend on their structural properties and atomic-level interactions. This chapter reviews our current knowledge of molecular architecture and interactions with the aim of identifying features and properties that fit the semaphorins and their receptors for biological function. Structural analyses of the hallmark sema domain in semaphorins have revealed a seven-bladed “-propeller with distinctive elaborations that mediate dimerization as well as receptor binding. The plexins, the major family of semaphorin receptors, are also distinguished by the presence of an Nterminal sema domain in their ectodomain. In plexins the sema domain fold is modified to serve as a monomeric platform for interactions with semaphorin ligands and co-receptors. In the recognition complex between semaphorin and plexin, the dimeric semaphorin acts as a crosslink to juxtapose two plexin receptors. The role of extracellular dimerization in triggering signaling appears to be mirrored inside the cell by dimerization-driven activation of the plexin cytoplasmic segment. The architecture of the cytoplasmic segment is novel in comprising a small RhoGTPasebinding domain inserted into a GTPase-activating protein (GAP)-type topology. The functional properties of this unique signal transducer are beginning to emerge, but the mode of signaling is one of many aspects of the semaphorin–plexin system that still pose fascinating questions. In addition to surveying our current state of knowledge, this chapter delineates the limits of our understanding of molecular mechanism in semaphorin biology.

Original publication

DOI

10.1007/978-4-431-54385-5_5

Type

Chapter

Book title

Semaphorins: A Diversity of Emerging Physiological and Pathological Activities

Publication Date

01/01/2015

Pages

87 - 107